Chapter 22 : The Role and Function of Fcγ Receptors on Myeloid Cells

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

The Role and Function of Fcγ Receptors on Myeloid Cells, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap22-1.gif /docserver/preview/fulltext/10.1128/9781555819194/9781555819187_Chap22-2.gif


A key determinant for the survival of an organism is the ability to recognize and respond to invading pathogens without damaging host tissues. This is accomplished largely by the concerted activity of the innate and adaptive branches of the immune system, which efficiently eliminate invading pathogens and restore tissue homeostasis. An initial step in the generation of robust immune responses is the recognition of pathogens by host cells, triggering subsequent immune cell activation and induction of proinflammatory responses. This initial recognition is facilitated via pathogen-associated molecular patterns (PAMPs) that represent highly conserved molecular structures uniquely found in bacterial, viral, and fungal pathogens but not in host tissues. Such structures include peptidoglycans, zymosan, lipopolysaccharides, flagellin, double-stranded and single-stranded RNA, and CpG-containing DNA ( ). So far, an ever increasing number of receptors with the capacity to sense and respond to these PAMPs have been identified and are broadly categorized into distinct receptor families: Toll-like receptors (TLRs), RIG-I (retinoic acid-inducible gene I)-like receptors, NOD-like receptors, and C-type lectin receptors ( ). Following engagement, these pattern recognition receptors trigger the activation of several inflammatory pathways essential to mediate robust antimicrobial activity and induce sustained immune responses. This central role in immunity for pathogen sensing by innate immune receptors is also reflected by the emergence of pattern recognition receptors early in evolutionary history, as evidenced by the presence of highly conserved gene orthologs in invertebrate species. Additionally, genetic analysis of human and genes provided evidence for strong positive selection pressure in human populations, and several nonsynonymous polymorphisms influencing receptor activity have been associated with disease susceptibility ( ).

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Structure and composition of the Fc-associated N-linked glycan regulates binding to type I and type II FcγRs. An N-linked glycan structure is attached at the C2 domain of each of the two heavy chains of IgG and consists of a core heptasaccharide structure that is composed of fucose, galactose, -acetylglucosamine, and sialic acid residues. The structure and composition of this Fc-associated glycan determine binding specificity and affinity of the IgG Fc domain for different types of FcγRs. Several glycoform combinations exist with distinct binding capacity to interact with type I and type II FcγRs.

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Overview of type I and type II FcγR structure and expression pattern in myeloid cell populations. Structural characteristics of type I and type II FcγRs. Type I FcγRs belong to the Ig receptor superfamily and are composed of two or three extracellular Ig-like domains that interact with the IgG Fc domain at the hinge-proximal region of the C2 domain. Type II FcγRs comprise DC-SIGN and CD23, both C-type lectin receptors, which bind sialylated Fc IgGs. Expression pattern of type I and type II FcγRs in myeloid leukocyte populations. The expression of several FcγRs is determined by cell differentiation status and is regulated by cytokines like IL-4 and IFN-γ.

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Effector functions and processes that are regulated by Fc-FcγR interactions. Engagement of type I and type II FcγRs by the Fc domain of IgG initiates signaling cascades with diverse proinflammatory, anti-inflammatory, and immunomodulatory consequences on myeloid cells, including granulocytes, monocytes, macrophages, DCs, and platelets. ROS, reactive oxygen species.

Citation: Bournazos S, Wang T, Ravetch J. 2017. The Role and Function of Fcγ Receptors on Myeloid Cells, p 407-427. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0045-2016
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Netea MG,, Wijmenga C,, O’Neill LA . 2012. Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol 13 : 535542.
2. Gack MU . 2014. Mechanisms of RIG-I-like receptor activation and manipulation by viral pathogens. J Virol 88 : 52135216.
3. Yoo JS,, Kato H,, Fujita T . 2014. Sensing viral invasion by RIG-I like receptors. Curr Opin Microbiol 20 : 131138.
4. Sparrer KM,, Gack MU . 2015. Intracellular detection of viral nucleic acids. Curr Opin Microbiol 26 : 19.
5. Pincetic A,, Bournazos S,, DiLillo DJ,, Maamary J,, Wang TT,, Dahan R,, Fiebiger BM,, Ravetch JV . 2014. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat Immunol 15 : 707716.
6. Anthony RM,, Wermeling F,, Ravetch JV . 2012. Novel roles for the IgG Fc glycan. Ann N Y Acad Sci 1253 : 170180.
7. Borrok MJ,, Jung ST,, Kang TH,, Monzingo AF,, Georgiou G . 2012. Revisiting the role of glycosylation in the structure of human IgG Fc. ACS Chem Biol 7 : 15961602.
8. Ahmed AA,, Giddens J,, Pincetic A,, Lomino JV,, Ravetch JV,, Wang LX,, Bjorkman PJ . 2014. Structural characterization of anti-inflammatory immunoglobulin G Fc proteins. J Mol Biol 426 : 31663179.
9. Sondermann P,, Pincetic A,, Maamary J,, Lammens K,, Ravetch JV . 2013. General mechanism for modulating immunoglobulin effector function. Proc Natl Acad Sci U S A 110 : 98689872.
10. Bournazos S,, Ravetch JV . 2015. Fcγ receptor pathways during active and passive immunization. Immunol Rev 268 : 88103.
11. Narciso JE,, Uy ID,, Cabang AB,, Chavez JF,, Pablo JL,, Padilla-Concepcion GP,, Padlan EA . 2011. Analysis of the antibody structure based on high-resolution crystallographic studies. N Biotechnol 28 : 435447.
12. Krapp S,, Mimura Y,, Jefferis R,, Huber R,, Sondermann P . 2003. Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol 325 : 979989.
13. Teplyakov A,, Zhao Y,, Malia TJ,, Obmolova G,, Gilliland GL . 2013. IgG2 Fc structure and the dynamic features of the IgG CH2-CH3 interface. Mol Immunol 56 : 131139.
14. Albert H,, Collin M,, Dudziak D,, Ravetch JV,, Nimmerjahn F . 2008. In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner. Proc Natl Acad Sci U S A 105 : 1500515009.
15. Lux A,, Nimmerjahn F . 2011. Impact of differential glycosylation on IgG activity. Adv Exp Med Biol 780 : 113124.
16. Nimmerjahn F,, Ravetch JV . 2005. Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science 310 : 15101512.
17. Nimmerjahn F,, Anthony RM,, Ravetch JV . 2007. Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci U S A 104 : 84338437.
18. Anthony RM,, Nimmerjahn F,, Ashline DJ,, Reinhold VN,, Paulson JC,, Ravetch JV . 2008. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320 : 373376.
19. Baudino L,, Shinohara Y,, Nimmerjahn F,, Furukawa J,, Nakata M,, Martínez-Soria E,, Petry F,, Ravetch JV,, Nishimura S,, Izui S . 2008. Crucial role of aspartic acid at position 265 in the CH2 domain for murine IgG2a and IgG2b Fc-associated effector functions. J Immunol 181 : 66646669.
20. Ferrara C,, Grau S,, Jäger C,, Sondermann P,, Brünker P,, Waldhauer I,, Hennig M,, Ruf A,, Rufer AC,, Stihle M,, Umaña P,, Benz J . 2011. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcγRIII and antibodies lacking core fucose. Proc Natl Acad Sci U S A 108 : 1266912674.
21. Shinkawa T,, Nakamura K,, Yamane N,, Shoji-Hosaka E,, Kanda Y,, Sakurada M,, Uchida K,, Anazawa H,, Satoh M,, Yamasaki M,, Hanai N,, Shitara K . 2003. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 278 : 34663473.
22. Cramer P,, Hallek M,, Eichhorst B . 2016. State-of-the-art treatment and novel agents in chronic lymphocytic leukemia. Oncol Res Treat 39 : 2532.
23. Goede V,, Fischer K,, Busch R,, Engelke A,, Eichhorst B,, Wendtner CM,, Chagorova T,, de la Serna J,, Dilhuydy MS,, Illmer T,, Opat S,, Owen CJ,, Samoylova O,, Kreuzer KA,, Stilgenbauer S,, Döhner H,, Langerak AW,, Ritgen M,, Kneba M,, Asikanius E,, Humphrey K,, Wenger M,, Hallek M . 2014. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 370 : 11011110.
24. Natsume A,, Niwa R,, Satoh M . 2009. Improving effector functions of antibodies for cancer treatment: enhancing ADCC and CDC. Drug Des Devel Ther 3 : 716.
25. Hiatt A,, Bohorova N,, Bohorov O,, Goodman C,, Kim D,, Pauly MH,, Velasco J,, Whaley KJ,, Piedra PA,, Gilbert BE,, Zeitlin L . 2014. Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy. Proc Natl Acad Sci U S A 111 : 59925997.
26. Shields RL,, Lai J,, Keck R,, O’Connell LY,, Hong K,, Meng YG,, Weikert SH,, Presta LG . 2002. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity. J Biol Chem 277 : 2673326740.
27. Kaneko Y,, Nimmerjahn F,, Ravetch JV . 2006. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313 : 670673.
28. Anthony RM,, Wermeling F,, Karlsson MC,, Ravetch JV . 2008. Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci U S A 105 : 1957119578.
29. Bournazos S,, Woof JM,, Hart SP,, Dransfield I . 2009. Functional and clinical consequences of Fc receptor polymorphic and copy number variants. Clin Exp Immunol 157 : 244254.
30. Nimmerjahn F,, Ravetch JV . 2006. Fcγ receptors: old friends and new family members. Immunity 24 : 1928.
31. Shields RL,, Namenuk AK,, Hong K,, Meng YG,, Rae J,, Briggs J,, Xie D,, Lai J,, Stadlen A,, Li B,, Fox JA,, Presta LG . 2001. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J Biol Chem 276 : 65916604.
32. Sondermann P,, Huber R,, Oosthuizen V,, Jacob U . 2000. The 3.2-Å crystal structure of the human IgG1 Fc fragment-FcγRIII complex. Nature 406 : 267273.
33. Sondermann P,, Kaiser J,, Jacob U . 2001. Molecular basis for immune complex recognition: a comparison of Fc-receptor structures. J Mol Biol 309 : 737749.
34. Qiu WQ,, de Bruin D,, Brownstein BH,, Pearse R,, Ravetch JV . 1990. Organization of the human and mouse low-affinity FcγR genes: duplication and recombination. Science 248 : 732735.
35. Su K,, Wu J,, Edberg JC,, McKenzie SE,, Kimberly RP . 2002. Genomic organization of classical human low-affinity Fcγ receptor genes. Genes Immun 3(Suppl 1): S51S56.
36. Ernst LK,, van de Winkel JG,, Chiu IM,, Anderson CL . 1992. Three genes for the human high affinity Fc receptor for IgG (FcγRI) encode four distinct transcription products. J Biol Chem 267 : 1569215700.
37. Ernst LK,, Duchemin AM,, Miller KL,, Anderson CL . 1998. Molecular characterization of six variant Fcγ receptor class I (CD64) transcripts. Mol Immunol 35 : 943954.
38. van Vugt MJ,, Reefman E,, Zeelenberg I,, Boonen G,, Leusen JH,, van de Winkel JG . 1999. The alternatively spliced CD64 transcript FcγRIb2 does not specify a surface-expressed isoform. Eur J Immunol 29 : 143149.
39. Kiyoshi M,, Caaveiro JM,, Kawai T,, Tashiro S,, Ide T,, Asaoka Y,, Hatayama K,, Tsumoto K . 2015. Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI. Nat Commun 6 : 6866. doi:10.1038/ncomms7866.
40. Duchemin AM,, Ernst LK,, Anderson CL . 1994. Clustering of the high affinity Fc receptor for immunoglobulin G (FcγRI) results in phosphorylation of its associated γ-chain. J Biol Chem 269 : 1211112117.
41. Ernst LK,, Duchemin AM,, Anderson CL . 1993. Association of the high-affinity receptor for IgG (FcγRI) with the γ subunit of the IgE receptor. Proc Natl Acad Sci U S A 90 : 60236027.
42. Indik ZK,, Hunter S,, Huang MM,, Pan XQ,, Chien P,, Kelly C,, Levinson AI,, Kimberly RP,, Schreiber AD . 1994. The high affinity Fcγ receptor (CD64) induces phagocytosis in the absence of its cytoplasmic domain: the γ subunit of FcγRIIIA imparts phagocytic function to FcγRI. Exp Hematol 22 : 599606.
43. van Vugt MJ,, Heijnen AF,, Capel PJ,, Park SY,, Ra C,, Saito T,, Verbeek JS,, van de Winkel JG . 1996. FcR γ-chain is essential for both surface expression and function of human FcγRI (CD64) in vivo. Blood 87 : 35933599.
44. Masuda M,, Roos D . 1993. Association of all three types of FcγR (CD64, CD32, and CD16) with a γ-chain homodimer in cultured human monocytes. J Immunol 151 : 71887195.
45. Li Y,, Lee PY,, Sobel ES,, Narain S,, Satoh M,, Segal MS,, Reeves WH,, Richards HB . 2009. Increased expression of FcγRI/CD64 on circulating monocytes parallels ongoing inflammation and nephritis in lupus. Arthritis Res Ther 11 : R6. doi:10.1186/ar2590.
46. Uciechowski P,, Schwarz M,, Gessner JE,, Schmidt RE,, Resch K,, Radeke HH . 1998. IFN-gamma induces the high-affinity Fc receptor I for IgG (CD64) on human glomerular mesangial cells. Eur J Immunol 28 : 29282935.
47. Maxwell KF,, Powell MS,, Hulett MD,, Barton PA,, McKenzie IF,, Garrett TP,, Hogarth PM . 1999. Crystal structure of the human leukocyte Fc receptor, FcγRIIa. Nat Struct Biol 6 : 437442.
48. Radaev S,, Motyka S,, Fridman WH,, Sautes-Fridman C,, Sun PD . 2001. The structure of a human type III Fcγ receptor in complex with Fc. J Biol Chem 276 : 1646916477.
49. Radaev S,, Sun P . 2002. Recognition of immunoglobulins by Fcγ receptors. Mol Immunol 38 : 10731083.
50. Maenaka K,, van der Merwe PA,, Stuart DI,, Jones EY,, Sondermann P . 2001. The human low affinity Fcγ receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties. J Biol Chem 276 : 4489844904.
51. Ravetch JV,, Bolland S . 2001. IgG Fc receptors. Annu Rev Immunol 19 : 275290.
52. Brooks DG,, Qiu WQ,, Luster AD,, Ravetch JV . 1989. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes. J Exp Med 170 : 13691385.
53. Lewis VA,, Koch T,, Plutner H,, Mellman I . 1986. A complementary DNA clone for a macrophage-lymphocyte Fc receptor. Nature 324 : 372375.
54. Latour S,, Fridman WH,, Daëron M . 1996. Identification, molecular cloning, biologic properties, and tissue distribution of a novel isoform of murine low-affinity IgG receptor homologous to human Fc gamma RIIB1. J Immunol 157 : 189197.
55. Hibbs ML,, Bonadonna L,, Scott BM,, McKenzie IF,, Hogarth PM . 1988. Molecular cloning of a human immunoglobulin G Fc receptor. Proc Natl Acad Sci U S A 85 : 22402244.
56. Metes D,, Ernst LK,, Chambers WH,, Sulica A,, Herberman RB,, Morel PA . 1998. Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcγRIIC gene. Blood 91 : 23692380.
57. Ernst LK,, Metes D,, Herberman RB,, Morel PA . 2002. Allelic polymorphisms in the FcγRIIC gene can influence its function on normal human natural killer cells. J Mol Med (Berl) 80 : 248257.
58. Bournazos S,, DiLillo DJ,, Ravetch JV . 2015. The role of Fc-FcγR interactions in IgG-mediated microbial neutralization. J Exp Med 212 : 13611369.
59. Hibbs ML,, Selvaraj P,, Carpén O,, Springer TA,, Kuster H,, Jouvin MH,, Kinet JP . 1989. Mechanisms for regulating expression of membrane isoforms of Fc gamma RIII (CD16). Science 246 : 16081611.
60. Masuda M,, Verhoeven AJ,, Roos D . 1993. Tyrosine phosphorylation of a gamma-chain homodimer associated with Fc gamma RIII (CD16) in cultured human monocytes. J Immunol 151 : 63826388.
61. Unkeless JC,, Shen Z,, Lin CW,, DeBeus E . 1995. Function of human Fc gamma RIIA and Fc gamma RIIIB. Semin Immunol 7 : 3744.
62. Selvaraj P,, Carpén O,, Hibbs ML,, Springer TA . 1989. Natural killer cell and granulocyte Fc gamma receptor III (CD16) differ in membrane anchor and signal transduction. J Immunol 143 : 32833288.
63. Edberg JC,, Kimberly RP . 1994. Modulation of Fc gamma and complement receptor function by the glycosyl-phosphatidylinositol-anchored form of Fc gamma RIII. J Immunol 152 : 58265835.
64. Smith P,, DiLillo DJ,, Bournazos S,, Li F,, Ravetch JV . 2012. Mouse model recapitulating human Fcγ receptor structural and functional diversity. Proc Natl Acad Sci U S A 109 : 61816186.
65. Passlick B,, Flieger D,, Ziegler-Heitbrock HW . 1989. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74 : 25272534.
66. Clynes RA,, Towers TL,, Presta LG,, Ravetch JV . 2000. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6 : 443446.
67. DiLillo DJ,, Ravetch JV . 2015. Differential Fc-receptor engagement drives an anti-tumor vaccinal effect. Cell 161 : 10351045.
68. Amigorena S,, Bonnerot C,, Drake JR,, Choquet D,, Hunziker W,, Guillet JG,, Webster P,, Sautes C,, Mellman I,, Fridman WH . 1992. Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes. Science 256 : 18081812.
69. Amigorena S,, Salamero J,, Davoust J,, Fridman WH,, Bonnerot C . 1992. Tyrosine-containing motif that transduces cell activation signals also determines internalization and antigen presentation via type III receptors for IgG. Nature 358 : 337341.
70. Cosson P,, Lankford SP,, Bonifacino JS,, Klausner RD . 1991. Membrane protein association by potential intramembrane charge pairs. Nature 351 : 414416.
71. Orloff DG,, Ra CS,, Frank SJ,, Klausner RD,, Kinet JP . 1990. Family of disulphide-linked dimers containing the ζ and η chains of the T-cell receptor and the γ chain of Fc receptors. Nature 347 : 189191.
72. Nimmerjahn F,, Ravetch JV . 2008. Fcγ receptors as regulators of immune responses. Nat Rev Immunol 8 : 3447.
73. Segal DM,, Taurog JD,, Metzger H . 1977. Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation. Proc Natl Acad Sci U S A 74 : 29932997.
74. Kulczycki A Jr,, Metzger H . 1974. The interaction of IgE with rat basophilic leukemia cells. II. Quantitative aspects of the binding reaction. J Exp Med 140 : 16761695.
75. Ishizaka T,, Ishizaka K . 1978. Triggering of histamine release from rat mast cells by divalent antibodies against IgE-receptors. J Immunol 120 : 800805.
76. Salmon JE,, Millard SS,, Brogle NL,, Kimberly RP . 1995. Fcγ receptor IIIb enhances Fcγ receptor IIa function in an oxidant-dependent and allele-sensitive manner. J Clin Invest 95 : 28772885.
77. Sobota A,, Strzelecka-Kiliszek A,, Gładkowska E,, Yoshida K,, Mrozińska K,, Kwiatkowska K . 2005. Binding of IgG-opsonized particles to FcγR is an active stage of phagocytosis that involves receptor clustering and phosphorylation. J Immunol 175 : 44504457.
78. Durden DL,, Liu YB . 1994. Protein-tyrosine kinase p72syk in FcγRI receptor signaling. Blood 84 : 21022108.
79. Durden DL,, Kim HM,, Calore B,, Liu Y . 1995. The Fc gamma RI receptor signals through the activation of hck and MAP kinase. J Immunol 154 : 40394047.
80. Eiseman E,, Bolen JB . 1992. Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature 355 : 7880.
81. Jouvin MH,, Adamczewski M,, Numerof R,, Letourneur O,, Vallé A,, Kinet JP . 1994. Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor. J Biol Chem 269 : 59185925.
82. Pignata C,, Prasad KV,, Robertson MJ,, Levine H,, Rudd CE,, Ritz J . 1993. Fc gamma RIIIA-mediated signaling involves src-family lck in human natural killer cells. J Immunol 151 : 67946800.
83. Swanson JA,, Hoppe AD . 2004. The coordination of signaling during Fc receptor-mediated phagocytosis. J Leukoc Biol 76 : 10931103.
84. Hamawy MM,, Minoguchi K,, Swaim WD,, Mergenhagen SE,, Siraganian RP . 1995. A 77-kDa protein associates with pp125FAK in mast cells and becomes tyrosine-phosphorylated by high affinity IgE receptor aggregation. J Biol Chem 270 : 1230512309.
85. García-García E,, Sánchez-Mejorada G,, Rosales C . 2001. Phosphatidylinositol 3-kinase and ERK are required for NF-κB activation but not for phagocytosis. J Leukoc Biol 70 : 649658.
86. Kanakaraj P,, Duckworth B,, Azzoni L,, Kamoun M,, Cantley LC,, Perussia B . 1994. Phosphatidylinositol-3 kinase activation induced upon FcγRIIIA-ligand interaction. J Exp Med 179 : 551558.
87. Ninomiya N,, Hazeki K,, Fukui Y,, Seya T,, Okada T,, Hazeki O,, Ui M . 1994. Involvement of phosphatidylinositol 3-kinase in Fcγ receptor signaling. J Biol Chem 269 : 2273222737.
88. Sánchez-Mejorada G,, Rosales C . 1998. Fcγ receptor-mediated mitogen-activated protein kinase activation in monocytes is independent of Ras. J Biol Chem 273 : 2761027619.
89. Aramburu J,, Azzoni L,, Rao A,, Perussia B . 1995. Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding. J Exp Med 182 : 801810.
90. Bracke M,, Coffer PJ,, Lammers JW,, Koenderman L . 1998. Analysis of signal transduction pathways regulating cytokine-mediated Fc receptor activation on human eosinophils. J Immunol 161 : 67686774.
91. Zhou MJ,, Brown EJ . 1994. CR3 (Mac-1, αMβ2, CD11b/CD18) and FcγRIII cooperate in generation of a neutrophil respiratory burst: requirement for FcγRIII and tyrosine phosphorylation. J Cell Biol 125 : 14071416.
92. Muta T,, Kurosaki T,, Misulovin Z,, Sanchez M,, Nussenzweig MC,, Ravetch JV . 1994. A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling. Nature 368 : 7073.
93. Pearse RN,, Kawabe T,, Bolland S,, Guinamard R,, Kurosaki T,, Ravetch JV . 1999. SHIP recruitment attenuates FcγRIIB-induced B cell apoptosis. Immunity 10 : 753760.
94. Ono M,, Bolland S,, Tempst P,, Ravetch JV . 1996. Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FcγRIIB. Nature 383 : 263266.
95. Ono M,, Okada H,, Bolland S,, Yanagi S,, Kurosaki T,, Ravetch JV . 1997. Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 90 : 293301.
96. Bolland S,, Yim YS,, Tus K,, Wakeland EK,, Ravetch JV . 2002. Genetic modifiers of systemic lupus erythematosus in FcγRIIB–/– mice. J Exp Med 195 : 11671174.
97. Bolland S,, Ravetch JV . 2000. Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity 13 : 277285.
98. Desai DD,, Harbers SO,, Flores M,, Colonna L,, Downie MP,, Bergtold A,, Jung S,, Clynes R . 2007. Fcγ receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses. J Immunol 178 : 62176226.
99. Takai T,, Ono M,, Hikida M,, Ohmori H,, Ravetch JV . 1996. Augmented humoral and anaphylactic responses in FcγRII-deficient mice. Nature 379 : 346349.
100. Yuasa T,, Kubo S,, Yoshino T,, Ujike A,, Matsumura K,, Ono M,, Ravetch JV,, Takai T . 1999. Deletion of Fcγ receptor IIB renders H-2b mice susceptible to collagen-induced arthritis. J Exp Med 189 : 187194.
101. Floto RA,, Clatworthy MR,, Heilbronn KR,, Rosner DR,, MacAry PA,, Rankin A,, Lehner PJ,, Ouwehand WH,, Allen JM,, Watkins NA,, Smith KG . 2005. Loss of function of a lupus-associated FcγRIIb polymorphism through exclusion from lipid rafts. Nat Med 11 : 10561058.
102. Kono H,, Kyogoku C,, Suzuki T,, Tsuchiya N,, Honda H,, Yamamoto K,, Tokunaga K,, Honda Z . 2005. FcγRIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling. Hum Mol Genet 14 : 28812892.
103. Blank MC,, Stefanescu RN,, Masuda E,, Marti F,, King PD,, Redecha PB,, Wurzburger RJ,, Peterson MG,, Tanaka S,, Pricop L . 2005. Decreased transcription of the human FCGR2B gene mediated by the -343 G/C promoter polymorphism and association with systemic lupus erythematosus. Hum Genet 117 : 220227.
104. Su K,, Wu J,, Edberg JC,, Li X,, Ferguson P,, Cooper GS,, Langefeld CD,, Kimberly RP . 2004. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcγRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J Immunol 172 : 71867191.
105. Wang TT,, Maamary J,, Tan GS,, Bournazos S,, Davis CW,, Krammer F,, Schlesinger SJ,, Palese P,, Ahmed R,, Ravetch JV . 2015. Anti-HA glycoforms drive B cell affinity selection and determine influenza vaccine efficacy. Cell 162 : 160169.
106. Jellusova J,, Nitschke L . 2012. Regulation of B cell functions by the sialic acid-binding receptors Siglec-G and CD22. Front Immunol 2 : 96. doi:10.3389/fimmu.2011.00096.
107. Schwab I,, Seeling M,, Biburger M,, Aschermann S,, Nitschke L,, Nimmerjahn F . 2012. B cells and CD22 are dispensable for the immediate anti-inflammatory activity of intravenous immunoglobulins in vivo. Eur J Immunol 42 : 33023309.
108. Böhm S,, Kao D,, Nimmerjahn F . 2014. Sweet and sour: the role of glycosylation for the anti-inflammatory activity of immunoglobulin G. Curr Top Microbiol Immunol 382 : 393417.
109. Anthony RM,, Kobayashi T,, Wermeling F,, Ravetch JV . 2011. Intravenous gammaglobulin suppresses inflammation through a novel TH2 pathway. Nature 475 : 110113.
110. Fiebiger BM,, Maamary J,, Pincetic A,, Ravetch JV . 2015. Protection in antibody- and T cell-mediated autoimmune diseases by anti-inflammatory IgG Fcs requires type II FcRs. Proc Natl Acad Sci U S A 112 : E2385E2394.
111. Soilleux EJ . 2003. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe? Clin Sci (Lond) 104 : 437446.
112. Borthakur S,, Andrejeva G,, McDonnell JM . 2011. Basis of the intrinsic flexibility of the Cε3 domain of IgE. Biochemistry 50 : 46084614.
113. Dhaliwal B,, Yuan D,, Pang MO,, Henry AJ,, Cain K,, Oxbrow A,, Fabiane SM,, Beavil AJ,, McDonnell JM,, Gould HJ,, Sutton BJ . 2012. Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcεRI. Proc Natl Acad Sci U S A 109 : 1268612691.
114. Yokota A,, Kikutani H,, Tanaka T,, Sato R,, Barsumian EL,, Suemura M,, Kishimoto T . 1988. Two species of human Fc epsilon receptor II (FcεRII/CD23): tissue-specific and IL-4-specific regulation of gene expression. Cell 55 : 611618.
115. Weskamp G,, Ford JW,, Sturgill J,, Martin S,, Docherty AJ,, Swendeman S,, Broadway N,, Hartmann D,, Saftig P,, Umland S,, Sehara-Fujisawa A,, Black RA,, Ludwig A,, Becherer JD,, Conrad DH,, Blobel CP . 2006. ADAM10 is a principal ‘sheddase’ of the low-affinity immunoglobulin E receptor CD23. Nat Immunol 7 : 12931298.
116. Regnault A,, Lankar D,, Lacabanne V,, Rodriguez A,, Théry C,, Rescigno M,, Saito T,, Verbeek S,, Bonnerot C,, Ricciardi-Castagnoli P,, Amigorena S . 1999. Fcγ receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 189 : 371380.
117. Jakus Z,, Berton G,, Ligeti E,, Lowell CA,, Mócsai A . 2004. Responses of neutrophils to anti-integrin antibodies depends on costimulation through low affinity FcγRs: full activation requires both integrin and nonintegrin signals. J Immunol 173 : 20682077.
118. Mócsai A,, Abram CL,, Jakus Z,, Hu Y,, Lanier LL,, Lowell CA . 2006. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol 7 : 13261333.
119. Dale DC,, Boxer L,, Liles WC . 2008. The phagocytes: neutrophils and monocytes. Blood 112 : 935945.
120. Nathan C . 2006. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6 : 173182.
121. Hampton MB,, Kettle AJ,, Winterbourn CC . 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92 : 30073017.
122. Martyn KD,, Kim MJ,, Quinn MT,, Dinauer MC,, Knaus UG . 2005. p21-activated kinase (Pak) regulates NADPH oxidase activation in human neutrophils. Blood 106 : 39623969.
123. Suh CI,, Stull ND,, Li XJ,, Tian W,, Price MO,, Grinstein S,, Yaffe MB,, Atkinson S,, Dinauer MC . 2006. The phosphoinositide-binding protein p40 phox activates the NADPH oxidase during FcγIIA receptor-induced phagocytosis. J Exp Med 203 : 19151925.
124. Yamauchi A,, Kim C,, Li S,, Marchal CC,, Towe J,, Atkinson SJ,, Dinauer MC . 2004. Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. J Immunol 173 : 59715979.
125. Nathan CF,, Brukner LH,, Silverstein SC,, Cohn ZA . 1979. Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide. J Exp Med 149 : 8499.
126. Nathan CF,, Silverstein SC,, Brukner LH,, Cohn ZA . 1979. Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med 149 : 100113.
127. Nathan C,, Cunningham-Bussel A . 2013. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol 13 : 349361.
128. Jönsson F,, Mancardi DA,, Albanesi M,, Bruhns P . 2013. Neutrophils in local and systemic antibody-dependent inflammatory and anaphylactic reactions. J Leukoc Biol 94 : 643656.
129. Sørensen O,, Arnljots K,, Cowland JB,, Bainton DF,, Borregaard N . 1997. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 90 : 27962803.
130. Cowland JB,, Johnsen AH,, Borregaard N . 1995. hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett 368 : 173176.
131. Egesten A,, Breton-Gorius J,, Guichard J,, Gullberg U,, Olsson I . 1994. The heterogeneity of azurophil granules in neutrophil promyelocytes: immunogold localization of myeloperoxidase, cathepsin G, elastase, proteinase 3, and bactericidal/permeability increasing protein. Blood 83 : 29852994.
132. Fouret P,, du Bois RM,, Bernaudin JF,, Takahashi H,, Ferrans VJ,, Crystal RG . 1989. Expression of the neutrophil elastase gene during human bone marrow cell differentiation. J Exp Med 169 : 833845.
133. Owen CA,, Campbell MA,, Boukedes SS,, Campbell EJ . 1995. Inducible binding of bioactive cathepsin G to the cell surface of neutrophils. A novel mechanism for mediating extracellular catalytic activity of cathepsin G. J Immunol 155 : 58035810.
134. Panyutich AV,, Hiemstra PS,, van Wetering S,, Ganz T . 1995. Human neutrophil defensin and serpins form complexes and inactivate each other. Am J Respir Cell Mol Biol 12 : 351357.
135. Gabay JE,, Almeida RP . 1993. Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin. Curr Opin Immunol 5 : 97102.
136. Ankersmit HJ,, Roth GA,, Moser B,, Zuckermann A,, Brunner M,, Rosin C,, Buchta C,, Bielek E,, Schmid W,, Jensen-Jarolim E,, Wolner E,, Boltz-Nitulescu G,, Volf I . 2003. CD32-mediated platelet aggregation in vitro by anti-thymocyte globulin: implication of therapy-induced in vivo thrombocytopenia. Am J Transplant 3 : 754759.
137. Pedicord DL,, Dicker I,, O’Neil K,, Breth L,, Wynn R,, Hollis GF,, Billheimer JT,, Stern AM,, Seiffert D . 2003. CD32-dependent platelet activation by a drug-dependent antibody to glycoprotein IIb/IIIa antagonists. Thromb Haemost 89 : 513521.
138. Poole A,, Gibbins JM,, Turner M,, van Vugt MJ,, van de Winkel JG,, Saito T,, Tybulewicz VL,, Watson SP . 1997. The Fc receptor γ-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO J 16 : 23332341.
139. Cerletti C,, Tamburrelli C,, Izzi B,, Gianfagna F,, de Gaetano G . 2012. Platelet-leukocyte interactions in thrombosis. Thromb Res 129 : 263266.
140. Gibbins JM,, Okuma M,, Farndale R,, Barnes M,, Watson SP . 1997. Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor γ-chain. FEBS Lett 413 : 255259.
141. Nieswandt B,, Bergmeier W,, Schulte V,, Rackebrandt K,, Gessner JE,, Zirngibl H . 2000. Expression and function of the mouse collagen receptor glycoprotein VI is strictly dependent on its association with the FcRγ chain. J Biol Chem 275 : 2399824002.
142. Martini F,, Riondino S,, Pignatelli P,, Gazzaniga PP,, Ferroni P,, Lenti L . 2002. Involvement of GD3 in platelet activation. A novel association with Fcγ receptor. Biochim Biophys Acta 1583 : 297304.
143. Hansson GK,, Hermansson A . 2011. The immune system in atherosclerosis. Nat Immunol 12 : 204212.
144. Steinhubl SR,, Moliterno DJ . 2005. The role of the platelet in the pathogenesis of atherothrombosis. Am J Cardiovasc Drugs 5 : 399408.
145. Bournazos S,, Rennie J,, Hart SP,, Fox KA,, Dransfield I . 2008. Monocyte functional responsiveness after PSGL-1-mediated platelet adhesion is dependent on platelet activation status. Arterioscler Thromb Vasc Biol 28 : 14911498.
146. Odin JA,, Edberg JC,, Painter CJ,, Kimberly RP,, Unkeless JC . 1991. Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor. Science 254 : 17851788.
147. Miettinen HM,, Rose JK,, Mellman I . 1989. Fc receptor isoforms exhibit distinct abilities for coated pit localization as a result of cytoplasmic domain heterogeneity. Cell 58 : 317327.
148. Bergtold A,, Desai DD,, Gavhane A,, Clynes R . 2005. Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity 23 : 503514.
149. Hoffmann E,, Kotsias F,, Visentin G,, Bruhns P,, Savina A,, Amigorena S . 2012. Autonomous phagosomal degradation and antigen presentation in dendritic cells. Proc Natl Acad Sci U S A 109 : 1455614561.
150. Bonnerot C,, Briken V,, Brachet V,, Lankar D,, Cassard S,, Jabri B,, Amigorena S . 1998. syk protein tyrosine kinase regulates Fc receptor γ-chain-mediated transport to lysosomes. EMBO J 17 : 46064616.
151. Dhodapkar KM,, Kaufman JL,, Ehlers M,, Banerjee DK,, Bonvini E,, Koenig S,, Steinman RM,, Ravetch JV,, Dhodapkar MV . 2005. Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells. Proc Natl Acad Sci U S A 102 : 29102915.
152. Kalergis AM,, Ravetch JV . 2002. Inducing tumor immunity through the selective engagement of activating Fcγ receptors on dendritic cells. J Exp Med 195 : 16531659.
153. Takai T,, Li M,, Sylvestre D,, Clynes R,, Ravetch JV . 1994. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 76 : 519529.
154. Clynes R,, Ravetch JV . 1995. Cytotoxic antibodies trigger inflammation through Fc receptors. Immunity 3 : 2126.
155. Abboud N,, Chow SK,, Saylor C,, Janda A,, Ravetch JV,, Scharff MD,, Casadevall A . 2010. A requirement for FcγR in antibody-mediated bacterial toxin neutralization. J Exp Med 207 : 23952405.
156. Bournazos S,, Klein F,, Pietzsch J,, Seaman MS,, Nussenzweig MC,, Ravetch JV . 2014. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell 158 : 12431253.
157. DiLillo DJ,, Palese P,, Wilson PC,, Ravetch JV . 2016. Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo protection. J Clin Invest 126 : 605610.
158. DiLillo DJ,, Tan GS,, Palese P,, Ravetch JV . 2014. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo . Nat Med 20 : 143151.
159. Varshney AK,, Wang X,, Aguilar JL,, Scharff MD,, Fries BC . 2014. Isotype switching increases efficacy of antibody protection against staphylococcal enterotoxin B-induced lethal shock and Staphylococcus aureus sepsis in mice. MBio 5 : e01007-14. doi:10.1128/mBio.01007-14.
160. Weber S,, Tian H,, van Rooijen N,, Pirofski LA . 2012. A serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibody requires Fcγ receptor III and macrophages to mediate protection against pneumococcal pneumonia in mice. Infect Immun 80 : 13141322.
161. Sanford JE,, Lupan DM,, Schlageter AM,, Kozel TR . 1990. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide. Infect Immun 58 : 19191923.
162. Schlageter AM,, Kozel TR . 1990. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. Infect Immun 58 : 19141918.
163. Nimmerjahn F,, Lux A,, Albert H,, Woigk M,, Lehmann C,, Dudziak D,, Smith P,, Ravetch JV . 2010. FcγRIV deletion reveals its central role for IgG2a and IgG2b activity in vivo. Proc Natl Acad Sci U S A 107 : 1939619401.
164. Lu CL,, Murakowski DK,, Bournazos S,, Schoofs T,, Sarkar D,, Halper-Stromberg A,, Horwitz JA,, Nogueira L,, Golijanin J,, Gazumyan A,, Ravetch JV,, Caskey M,, Chakraborty AK,, Nussenzweig MC . 2016. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 352 : 10011004.
165. Cartron G,, Dacheux L,, Salles G,, Solal-Celigny P,, Bardos P,, Colombat P,, Watier H . 2002. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 99 : 754758.
166. Uchida J,, Hamaguchi Y,, Oliver JA,, Ravetch JV,, Poe JC,, Haas KM,, Tedder TF . 2004. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. J Exp Med 199 : 16591669.
167. Hamaguchi Y,, Xiu Y,, Komura K,, Nimmerjahn F,, Tedder TF . 2006. Antibody isotype-specific engagement of Fcγ receptors regulates B lymphocyte depletion during CD20 immunotherapy. J Exp Med 203 : 743753.
168. Boruchov AM,, Heller G,, Veri MC,, Bonvini E,, Ravetch JV,, Young JW . 2005. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J Clin Invest 115 : 29142923.
169. te Velde AA,, de Waal Malefijt R,, Huijbens RJ,, de Vries JE,, Figdor CG . 1992. IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL-4, and IL-10. J Immunol 149 : 40484052.
170. Guilliams M,, Bruhns P,, Saeys Y,, Hammad H,, Lambrecht BN . 2014. The function of Fcγ receptors in dendritic cells and macrophages. Nat Rev Immunol 14 : 94108.
171. Diaz de Ståhl T,, Heyman B . 2001. IgG2a-mediated enhancement of antibody responses is dependent on FcRγ+ bone marrow-derived cells. Scand J Immunol 54 : 495500.
172. Gordon S,, Plüddemann A,, Martinez Estrada F . 2014. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev 262 : 3655.
173. Mosser DM,, Edwards JP . 2008. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8 : 958969.
174. Clynes R,, Maizes JS,, Guinamard R,, Ono M,, Takai T,, Ravetch JV . 1999. Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J Exp Med 189 : 179185.
175. Sutterwala FS,, Noel GJ,, Clynes R,, Mosser DM . 1997. Selective suppression of interleukin-12 induction after macrophage receptor ligation. J Exp Med 185 : 19771985.
176. Dhodapkar KM,, Banerjee D,, Connolly J,, Kukreja A,, Matayeva E,, Veri MC,, Ravetch JV,, Steinman RM,, Dhodapkar MV . 2007. Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program. J Exp Med 204 : 13591369.
177. Brownlie RJ,, Lawlor KE,, Niederer HA,, Cutler AJ,, Xiang Z,, Clatworthy MR,, Floto RA,, Greaves DR,, Lyons PA,, Smith KG . 2008. Distinct cell-specific control of autoimmunity and infection by FcγRIIb. J Exp Med 205 : 883895.
178. Clatworthy MR,, Smith KG . 2004. FcγRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. J Exp Med 199 : 717723.
179. Karassa FB,, Trikalinos TA,, Ioannidis JP , FcgammaRIIa-SLE Meta-Analysis Investigators . 2002. Role of the Fcγ receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Arthritis Rheum 46 : 15631571.
180. Karassa FB,, Trikalinos TA,, Ioannidis JP . 2004. The role of FcγRIIA and IIIA polymorphisms in autoimmune diseases. Biomed Pharmacother 58 : 286291.
181. van der Pol WL,, Jansen MD,, Kuks JB,, de Baets M,, Leppers-van de Straat FG,, Wokke JH,, van de Winkel JG,, van den Berg LH . 2003. Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients. J Neuroimmunol 144 : 143147.
182. van der Pol WL,, van den Berg LH,, Scheepers RH,, van der Bom JG,, van Doorn PA,, van Koningsveld R,, van den Broek MC,, Wokke JH,, van de Winkel JG . 2000. IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barré syndrome. Neurology 54 : 16611665.
183. Lehrnbecher T,, Foster CB,, Zhu S,, Leitman SF,, Goldin LR,, Huppi K,, Chanock SJ . 1999. Variant genotypes of the low-affinity Fcγ receptors in two control populations and a review of low-affinity Fcγ receptor polymorphisms in control and disease populations. Blood 94 : 42204232.
184. Tackenberg B,, Jelcic I,, Baerenwaldt A,, Oertel WH,, Sommer N,, Nimmerjahn F,, Lünemann JD . 2009. Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci U S A 106 : 47884792.
185. Li X,, Gibson AW,, Kimberly RP . 2014. Human FcR polymorphism and disease. Curr Top Microbiol Immunol 382 : 275302.
186. Beppler J,, Koehler-Santos P,, Pasqualim G,, Matte U,, Alho CS,, Dias FS,, Kowalski TW,, Velasco IT,, Monteiro RC,, Pinheiro da Silva F . 2016. Fc gamma receptor IIA (CD32A) R131 polymorphism as a marker of genetic susceptibility to sepsis. Inflammation 39 : 518525.
187. Endeman H,, Cornips MC,, Grutters JC,, van den Bosch JM,, Ruven HJ,, van Velzen-Blad H,, Rijkers GT,, Biesma DH . 2009. The Fcγ receptor IIA-R/R131 genotype is associated with severe sepsis in community-acquired pneumonia. Clin Vaccine Immunol 16 : 10871090.
188. Salmon JE,, Edberg JC,, Brogle NL,, Kimberly RP . 1992. Allelic polymorphisms of human Fcγ receptor IIA and Fcγ receptor IIIB. Independent mechanisms for differences in human phagocyte function. J Clin Invest 89 : 12741281.
189. González D,, Castro OE,, Kourí G,, Perez J,, Martinez E,, Vazquez S,, Rosario D,, Cancio R,, Guzman MG . 2005. Classical dengue hemorrhagic fever resulting from two dengue infections spaced 20 years or more apart: Havana, Dengue 3 epidemic, 2001-2002. Int J Infect Dis 9 : 280285.
190. Kliks SC,, Nimmanitya S,, Nisalak A,, Burke DS . 1988. Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. Am J Trop Med Hyg 38 : 411419.
191. Beltramello M,, Williams KL,, Simmons CP,, Macagno A,, Simonelli L,, Quyen NT,, Sukupolvi-Petty S,, Navarro-Sanchez E,, Young PR,, de Silva AM,, Rey FA,, Varani L,, Whitehead SS,, Diamond MS,, Harris E,, Lanzavecchia A,, Sallusto F . 2010. The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity. Cell Host Microbe 8 : 271283.
192. Vaughn DW,, Green S,, Kalayanarooj S,, Innis BL,, Nimmannitya S,, Suntayakorn S,, Endy TP,, Raengsakulrach B,, Rothman AL,, Ennis FA,, Nisalak A . 2000. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis 181 : 29.
193. Halstead SB,, O’Rourke EJ . 1977. Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146 : 201217.
194. Moi ML,, Takasaki T,, Saijo M,, Kurane I . 2013. Dengue virus infection-enhancing activity of undiluted sera obtained from patients with secondary dengue virus infection. Trans R Soc Trop Med Hyg 107 : 5158.
195. Blackley S,, Kou Z,, Chen H,, Quinn M,, Rose RC,, Schlesinger JJ,, Coppage M,, Jin X . 2007. Primary human splenic macrophages, but not T or B cells, are the principal target cells for dengue virus infection in vitro. J Virol 81 : 1332513334.
196. Kou Z,, Lim JY,, Beltramello M,, Quinn M,, Chen H,, Liu S,, Martinez-Sobrido L,, Diamond MS,, Schlesinger JJ,, de Silva A,, Sallusto F,, Jin X . 2011. Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes. Virology 410 : 240247.
197. Flipse J,, Wilschut J,, Smit JM . 2013. Molecular mechanisms involved in antibody-dependent enhancement of dengue virus infection in humans. Traffic 14 : 2535.
198. Modhiran N,, Kalayanarooj S,, Ubol S . 2010. Subversion of innate defenses by the interplay between DENV and pre-existing enhancing antibodies: TLRs signaling collapse. PLoS Negl Trop Dis 4 : e924. doi:10.1371/journal.pntd.0000924.
199. Ubol S,, Phuklia W,, Kalayanarooj S,, Modhiran N . 2010. Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies. J Infect Dis 201 : 923935.
200. OhAinle M,, Balmaseda A,, Macalalad AR,, Tellez Y,, Zody MC,, Saborío S,, Nuñez A,, Lennon NJ,, Birren BW,, Gordon A,, Henn MR,, Harris E . 2011. Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity. Sci Transl Med 3 : 114ra128. doi:10.1126/scitranslmed.3003084.
201. Leitmeyer KC,, Vaughn DW,, Watts DM,, Salas R,, Villalobos I,, de Chacon,, Ramos C,, Rico-Hesse R . 1999. Dengue virus structural differences that correlate with pathogenesis. J Virol 73 : 47384747.
202. Balmaseda A,, Hammond SN,, Pérez L,, Tellez Y,, Saborío SI,, Mercado JC,, Cuadra R,, Rocha J,, Pérez MA,, Silva S,, Rocha C,, Harris E . 2006. Serotype-specific differences in clinical manifestations of dengue. Am J Trop Med Hyg 74 : 449456.
203. Rico-Hesse R,, Harrison LM,, Salas RA,, Tovar D,, Nisalak A,, Ramos C,, Boshell J,, de Mesa MT,, Nogueira RM,, da Rosa AT . 1997. Origins of dengue type 2 viruses associated with increased pathogenicity in the Americas. Virology 230 : 244