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Low-affinity Fcγ receptors, autoimmunity and infection

  • Lisa C. Willcocks (a1), Kenneth G.C. Smith (a1) and Menna R. Clatworthy (a1)


Low-affinity Fcγ receptors (FcγRs) mediate the effects of immunoglobulin G (IgG) antibodies on leukocytes, including recruitment to inflammatory lesions, phagocytosis, antibody-dependent cellular cytotoxicity, release of inflammatory mediators and regulation of B cell activation. These functions are an important part of the mammalian response to infection, but if deployed inappropriately can cause autoimmune disease. Although most FcγRs are activatory, there is also an inhibitory FcγR that, when bound to IgG immune complexes, is able to downregulate the effects of both the activatory FcγRs and the B cell receptor. This review discusses the role of the low-affinity FcγRs in a balanced immune response and how perturbations in FcγR function result in susceptibility to infection or autoimmunity.


Corresponding author

*Corresponding author: Menna R. Clatworthy, Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK. Tel: +44 1223 762639; Fax: +44 1223 762645; E-mail:


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1Nimmerjahn, F. and Ravetch, J.V. (2006) Fcgamma receptors: old friends and new family members. Immunity 24, 19-28
2Warmerdam, P.A. et al. (1993) The human low affinity immunoglobulin G Fc receptor IIC gene is a result of an unequal crossover event. Journal of Biological Chemistry 268, 7346-7349
3Qiu, W.Q. et al. (1990) Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science 248, 732-735
4Hughes, A.L. (1996) Gene duplication and recombination in the evolution of mammalian Fc receptors. Journal of Molecular Evolution 43, 4-10
5Freeman, J.L. et al. (2006) Copy number variation: new insights in genome diversity. Genome Research 16, 949-961
6Redon, R. et al. (2006) Global variation in copy number in the human genome. Nature 444, 444-454
7McCarroll, S.A. et al. (2008) Integrated detection and population-genetic analysis of SNPs and copy number variation. Nature Genetics 40, 1166-1174
8Stranger, B.E. et al. (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315, 848-853
9Mamtani, M. et al. (2008) CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Annals of the Rheumatic Diseases 67, 1076-1083
10McKinney, C. et al. (2008) Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis. Annals of the Rheumatic Diseases 67, 409-413
11Estivill, X. and Armengol, L. (2007) Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies. PLoS Genetics 3, 1787-1799
12Ravetch, J.V. and Kinet, J.P. (1991) Fc receptors. Annual Review of Immunology 9, 457-492
13Galon, J. et al. (1996) Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors. Journal of Immunology 157, 1184-1192
14Chuang, F.Y., Sassaroli, M. and Unkeless, J.C. (2000) Convergence of Fc gamma receptor IIA and Fc gamma receptor IIIB signaling pathways in human neutrophils. Journal of Immunology 164, 350-360
15Fernandes, M.J. et al. (2006) CD16b associates with high-density, detergent-resistant membranes in human neutrophils. Biochemical Journal 393, 351-359
16Reth, M. (1989) Antigen receptor tail clue. Nature 338, 383-384
17He, Y.W. et al. (1995) Expression and function of the gamma c subunit of the IL-2, IL-4, and IL-7 receptors. Distinct interaction of gamma c in the IL-4 receptor. Journal of Immunology 154, 1596-1605
18Duncan, A.R. et al. (1988) Localization of the binding site for the human high-affinity Fc receptor on IgG. Nature 332, 563-564
19Lund, J. et al. (1991) Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG. Journal of Immunology 147, 2657-2662
20Canfield, S.M. and Morrison, S.L. (1991) The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. Journal of Experimental Medicine 173, 1483-1491
21Jefferis, R., Lund, J. and Pound, J. (1990) Molecular definition of interaction sites on human IgG for Fc receptors (huFc gamma R). Molecular Immunology 27, 1237-1240
22Nimmerjahn, F. and Ravetch, J.V. (2008) Fcgamma receptors as regulators of immune responses. Nature Reviews. Immunology 8, 34-47
23Raju, T.S. (2008) Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Current Opinion in Immunology 20, 471-478
24Radaev, S. and Sun, P.D. (2001) Recognition of IgG by Fcgamma receptor. The role of Fc glycosylation and the binding of peptide inhibitors. Journal of Biological Chemistry 276, 16478-16483
25Ferrara, C. et al. (2006) The carbohydrate at FcgammaRIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms. Journal of Biological Chemistry 281, 5032-5036
26Bharadwaj, D. et al. (2001) Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis. Journal of Immunology 166, 6735-6741
27Bharadwaj, D. et al. (1999) The major receptor for C-reactive protein on leukocytes is fcgamma receptor II. Journal of Experimental Medicine 190, 585-590
28Kaplan, M.H. and Volanakis, J.E. (1974) Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. Journal of Immunology 112, 2135-2147
29Lu, J. et al. (2008) Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature 456, 989-992
30Bux, J. et al. (1997) Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb. Blood 89, 1027-1034
31Ravetch, J.V. and Nimmerjahn, F. (2008) Fc receptors and their role in immune regulation and inflammation. InFundamental Immunology (6th edn) (Paul, W.E., ed.), pp. 684-705, Lippincott Williams & Wilkins
32Nimmerjahn, F. et al. (2005) FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Immunity 23, 41-51
33Nimmerjahn, F. and Ravetch, J.V. (2005) Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310, 1510-1512
34Young, J.D., Ko, S.S. and Cohn, Z.A. (1984) The increase in intracellular free calcium associated with IgG gamma 2b/gamma 1 Fc receptor-ligand interactions: role in phagocytosis. Proceedings of the National Academy of Sciences of the United States of America 81, 5430-5434
35Titus, J.A. et al. (1987) Human K/natural killer cells targeted with hetero-cross-linked antibodies specifically lyse tumor cells in vitro and prevent tumor growth in vivo. Journal of Immunology 139, 3153-3158
36Amigorena, S. and Bonnerot, C. (1999) Fc receptors for IgG and antigen presentation on MHC class I and class II molecules. Seminars in Immunology 11, 385-390
37Regnault, A. et al. (1999) Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. Journal of Experimental Medicine 189, 371-380
38Floto, R.A. et al. (2005) Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts. Nature Medicine 11, 1056-1058
39Kono, H. et al. (2005) FcgammaRIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling. Human Molecular Genetics 14, 2881-2892
40Pritchard, N.R. et al. (2000) Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcgammaRII. Current Biology 10, 227-230
41Jiang, Y. et al. (2000) Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility. Immunogenetics 51, 429-435
42Su, K. et al. (2004) A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. Journal of Immunology 172, 7186-7191
43Blank, M.C. et al. (2005) Decreased transcription of the human FCGR2B gene mediated by the – 343 G/C promoter polymorphism and association with systemic lupus erythematosus. Human Genetics 117, 220-227
44Nambu, M. et al. (1989) Regulation of Fc gamma receptor expression and phagocytosis of a human monoblast cell line U937. Participation of cAMP and protein kinase C in the effects of IFN-gamma and phorbol ester. Journal of Immunology 143, 4158-4165
45Cameron, A.J. et al. (2002) Differentiation of the human monocyte cell line, U937, with dibutyryl cyclicAMP induces the expression of the inhibitory Fc receptor, FcgammaRIIb. Immunology Letters 83, 171-179
46Pricop, L. et al. (2001) Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines. Journal of Immunology 166, 531-537
47Grattage, L.P., McKenzie, I.F. and Hogarth, P.M. (1992) Effects of PMA, cytokines and dexamethasone on the expression of cell surface Fc receptors and mRNA in U937 cells. Immunology and Cell Biology 70, 97-105
48Rudge, E.U. et al. (2002) Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes CD22 and Fc gamma RII-mediated B cell suppression. Journal of Experimental Medicine 195, 1079-1085
49Ulgiati, D. and Holers, V.M. (2001) CR2/CD21 proximal promoter activity is critically dependent on a cell type-specific repressor. Journal of Immunology 167, 6912-6919
50Cines, D.B. and Blanchette, V.S. (2002) Immune thrombocytopenic purpura. New England Journal of Medicine 346, 995-1008
51Wakeland, E.K. et al. (2001) Delineating the genetic basis of systemic lupus erythematosus. Immunity 15, 397-408
52Boackle, S.A. et al. (2001) Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15, 775-785
53Wandstrat, A.E. et al. (2004) Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus. Immunity 21, 769-780
54Xiu, Y. et al. (2002) Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses. Journal of Immunology 169, 4340-4346
55Suzuki, Y. et al. (1998) Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis. Kidney International 54, 1166-1174
56Clynes, R. and Ravetch, J.V. (1995) Cytotoxic antibodies trigger inflammation through Fc receptors. Immunity 3, 21-26
57Kleinau, S., Martinsson, P. and Heyman, B. (2000) Induction and suppression of collagen-induced arthritis is dependent on distinct fcgamma receptors. Journal of Experimental Medicine 191, 1611-1616
58Nakamura, A. et al. (2000) Fcgamma receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: a novel murine model for autoimmune glomerular basement membrane disease. Journal of Experimental Medicine 191, 899-906
59Yuasa, T. et al. (1999) Deletion of fcgamma receptor IIB renders H-2(b) mice susceptible to collagen-induced arthritis. Journal of Experimental Medicine 189, 187-194
60Brownlie, R.J. et al. (2008) Distinct cell-specific control of autoimmunity and infection by FcgammaRIIb. Journal of Experimental Medicine 205, 883-895
61Bolland, S. and Ravetch, J.V. (2000) Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 13, 277-285
62McGaha, T.L., Sorrentino, B. and Ravetch, J.V. (2005) Restoration of tolerance in lupus by targeted inhibitory receptor expression. Science 307, 590-593
63Brauweiler, A.M. and Cambier, J.C. (2004) Autonomous SHIP-dependent FcgammaR signaling in pre-B cells leads to inhibition of cell migration and induction of cell death. Immunology Letters 92, 75-81
64Pearse, R.N. et al. (1999) SHIP recruitment attenuates Fc gamma RIIB-induced B cell apoptosis. Immunity 10, 753-760
65Xiang, Z. et al. (2007) FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis. Nature Immunology 8, 419-429
66Alarcon-Segovia, D. et al. (2005) Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort. Arthritis and Rheumatism 52, 1138-1147
67Block, S.R. et al. (1975) Studies of twins with systemic lupus erythematosus. A review of the literature and presentation of 12 additional sets. American Journal of Medicine 59, 533-552
68Sestak, A.L. et al. (2007) Current status of lupus genetics. Arthritis Research and Therapy 9, 210
69Rhodes, B. and Vyse, T.J. (2008) The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford) 47, 1603-1611
70Lehrnbecher, T. et al. (1999) Variant genotypes of the low-affinity Fcgamma receptors in two control populations and a review of low-affinity Fcgamma receptor polymorphisms in control and disease populations. Blood 94, 4220-4232
71Karassa, F.B., Trikalinos, T.A. and Ioannidis, J.P. (2002) Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Arthritis and Rheumatism 46, 1563-1571
72Harley, J.B. et al. (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nature Genetics 40, 204-210
73Gonzalez-Escribano, M.F. et al. (2002) FcgammaRIIA, FcgammaRIIIA and FcgammaRIIIB polymorphisms in Spanish patients with systemic lupus erythematosus. European Journal of Immunogenetics 29, 301-306
74Siriboonrit, U. et al. (2003) Association of Fcgamma receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 61, 374-383
75Aitman, T.J. et al. (2006) Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439, 851-855
76Fanciulli, M. et al. (2007) FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nature Genetics 39, 721-723
77Hollox, E.J., Detering, J.C. and Dehnugara, T. (2009) An integrated approach for measuring copy number variation at the FCGR3 (CD16) locus. Human Mutation 30, 477-484
78Willcocks, L.C. et al. (2008) Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake. Journal of Experimental Medicine 205, 1573-1582
79Kyogoku, C. et al. (2002) Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Arthritis and Rheumatism 46, 1242-1254
80Li, X. et al. (2003) A novel polymorphism in the Fcgamma receptor IIB (CD32B) transmembrane region alters receptor signaling. Arthritis and Rheumatism 48, 3242-3252
81Chu, Z.T. et al. (2004) Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Tissue Antigens 63, 21-27
82Kyogoku, C. et al. (2004) Association of Fcgamma receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: A family-based association study in Caucasians. Arthritis and Rheumatism 50, 671-673
83Magnusson, V. et al. (2004) Polymorphisms of the Fc gamma receptor type IIB gene are not associated with systemic lupus erythematosus in the Swedish population. Arthritis and Rheumatism 50, 1348-1350
84Morgan, M.D. et al. (2006) Anti-neutrophil cytoplasm-associated glomerulonephritis. Journal of the American Society of Nephrology 17, 1224-1234
85Kain, R. et al. (2008) Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nature Medicine 14, 1088-1096
86Dijstelbloem, H.M. et al. (1999) Fcgamma receptor polymorphisms in Wegener's granulomatosis: risk factors for disease relapse. Arthritis and Rheumatism 42, 1823-1827
87van der Pol, W. and van de Winkel, J.G. (1998) IgG receptor polymorphisms: risk factors for disease. Immunogenetics 48, 222-232
88Stegeman, C.A. et al. (1994) Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Annals of Internal Medicine 120, 12-17
89Tse, W.Y. et al. (1999) No association between neutrophil FcgammaRIIa allelic polymorphism and anti-neutrophil cytoplasmic antibody (ANCA)-positive systemic vasculitis. Clinical and Experimental Immunology 117, 198-205
90Menard, H.A. et al. (2000) Insights into rheumatoid arthritis derived from the Sa immune system. Arthritis Research 2, 429-432
91van Venrooij, W.J., van Beers, J.J. and Pruijn, G.J. (2008) Anti-CCP antibody, a marker for the early detection of rheumatoid arthritis. Annals of the New York Academy of Sciences 1143, 268-285
92Foster, C.B. et al. (2001) Polymorphisms in inflammatory cytokines and Fcgamma receptors in childhood chronic immune thrombocytopenic purpura: a pilot study. British Journal of Haematology 113, 596-599
93Fujimoto, T.T. et al. (2001) Involvement of Fc gamma receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura. British Journal of Haematology 115, 125-130
94Breunis, W.B. et al. (2008) Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood 111, 1029-1038
95van der Pol, W.L. et al. (2003) Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients. Journal of Neuroimmunology 144, 143-147
96Melms, A. et al. (1993) Acetylcholine receptor-specific T cells are present in the normal immune repertoire. A study with recombinant polypeptides of the human acetylcholine receptor alpha-subunit. Annals of the New York Academy of Sciences 681, 310-312
97Melms, A. et al. (1993) Specific immune complexes augment in vitro acetylcholine receptor-specific T-cell proliferation. Neurology 43, 583-588
98Hadden, R.D. et al. (2001) Preceding infections, immune factors, and outcome in Guillain-Barre syndrome. Neurology 56, 758-765
99Ogino, M., Orazio, N. and Latov, N. (1995) IgG anti-GM1 antibodies from patients with acute motor neuropathy are predominantly of the IgG1 and IgG3 subclasses. Journal of Neuroimmunology 58, 77-80
100van Sorge, N.M. et al. (2003) Anti-GM1 IgG antibodies induce leukocyte effector functions via Fcgamma receptors. Annals of Neurology 53, 570-579
101Vedeler, C.A. et al. (1991) IgG Fc receptor heterogeneity in human peripheral nerves. Acta Neurologica Scandinavica 84, 177-180
102van der Pol, W.L. et al. (2000) IgG receptor IIa alleles determine susceptibility and severity of Guillain-Barre syndrome. Neurology 54, 1661-1665
103Vedeler, C.A. et al. (2000) IgG Fc-receptor polymorphisms in Guillain-Barre syndrome. Neurology 55, 705-707
104Tackenberg, B. et al. (2009) Impaired inhibitory Fcgamma receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proceedings of the National Academy of Sciences of the United States of America 106, 4788-4792
105Noseworthy, J.H. et al. (2000) Multiple sclerosis. New England Journal of Medicine 343, 938-952
106Dasgupta, M.K. et al. (1982) Circulating immune complexes in multiple sclerosis: relation with disease activity. Neurology 32, 1000-1004
107Myhr, K.M. et al. (1999) Immunoglobulin G Fc-receptor (FcgammaR) IIA and IIIB polymorphisms related to disability in MS. Neurology 52, 1771-1776
108Nikseresht, A. et al. (2006) Investigation of Fcgamma RIIA and Fcgamma RIIIA polymorphism in movement disorders: a case control study. Iran Journal of Immunology 3, 136-141
109Ballow, M. (2002) Primary immunodeficiency disorders: antibody deficiency. Journal of Allergy and Clinical Immunology 109, 581-591
110Gjertsson, I., Kleinau, S. and Tarkowski, A. (2002) The impact of Fcgamma receptors on Staphylococcus aureus infection. Microbial Pathogenesis 33, 145-152
111Hellwig, S.M. et al. (2001) Targeting to Fcgamma receptors, but not CR3 (CD11b/CD18), increases clearance of Bordetella pertussis. Journal of Infectious Diseases 183, 871-879
112Ioan-Facsinay, A. et al. (2002) FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection. Immunity 16, 391-402
113Huber, V.C. et al. (2001) Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections. Journal of Immunology 166, 7381-7388
114Moore, T. et al. (2003) Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens. Journal of Infectious Diseases 188, 617-624
115Gray, C.A. and Lawrence, R.A. (2002) A role for antibody and Fc receptor in the clearance of Brugia malayi microfilariae. European Journal of Immunology 32, 1114-1120
116Yoneto, T. et al. (2001) A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection. Journal of Immunology 166, 6236-6241
117Clatworthy, M.R. et al. (2007) Systemic lupus erythematosus-associated defects in the inhibitory receptor FcgammaRIIb reduce susceptibility to malaria. Proceedings of the National Academy of Sciences of the United States of America 104, 7169-7174
118Clatworthy, M.R. and Smith, K.G.C. (2004) Fc{gamma}RIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. Journal of Experimental Medicine 199, 717-723
119Briles, D.E. et al. (1981) Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 streptococcus pneumoniae. Journal of Experimental Medicine 153, 694-705
120Mold, C., Rodic-Polic, B. and Du Clos, T.W. (2002) Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fc gamma receptors. Journal of Immunology 168, 6375-6381
121Rodriguez, M.E. et al. (1999) Crucial role of FcgammaRIIa (CD32) in assessment of functional anti-Streptococcus pneumoniae antibody activity in human sera. Journal of Infectious Diseases 179, 423-433
122Yee, A.M. et al. (2000) Association between FcgammaRIIa-R131 allotype and bacteremic pneumococcal pneumonia. Clinical Infectious Diseases 30, 25-28
123Yuan, F.F. et al. (2003) FcgammaRIIA polymorphisms in Streptococcus pneumoniae infection. Immunology and Cell Biology 81, 192-195
124Pathan, N., Faust, S.N. and Levin, M. (2003) Pathophysiology of meningococcal meningitis and septicaemia. Archives of Disease in Childhood 88, 601-607
125Bredius, R.G. et al. (1994) Role of neutrophil Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16) polymorphic forms in phagocytosis of human IgG1- and IgG3-opsonized bacteria and erythrocytes. Immunology 83, 624-630
126Fijen, C.A. et al. (2000) The role of Fcgamma receptor polymorphisms and C3 in the immune defence against Neisseria meningitidis in complement-deficient individuals. Clinical and Experimental Immunology 120, 338-345
127Bredius, R.G. et al. (1994) Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children. Journal of Infectious Diseases 170, 848-853
128Smith, I., Vedeler, C. and Halstensen, A. (2003) FcgammaRIIa and FcgammaRIIIb polymorphisms were not associated with meningococcal disease in Western Norway. Epidemiology and Infection 130, 193-199
129Platonov, A.E. et al. (1998) Association of human Fc gamma RIIa (CD32) polymorphism with susceptibility to and severity of meningococcal disease. Clinical Infectious Diseases 27, 746-750
130Domingo, P. et al. (2002) Associations between Fc gamma receptor IIA polymorphisms and the risk and prognosis of meningococcal disease. American Journal of Medicine 112, 19-25
131Domingo, P. et al. (2004) Relevance of genetically determined host factors to the prognosis of meningococcal disease. European Journal of Clinical Microbiology and Infectious Diseases 23, 634-637
132Schenkein, H.A., Barbour, S.E. and Tew, J.G. (2007) Cytokines and inflammatory factors regulating immunoglobulin production in aggressive periodontitis. Periodontology 2000 45, 113-127
133Loos, B.G. et al. (2003) Fcgamma receptor polymorphisms in relation to periodontitis. Journal of Clinical Periodontology 30, 595-602
134Chung, H.Y. et al. (2003) Gm (23) allotypes and Fcgamma receptor genotypes as risk factors for various forms of periodontitis. Journal of Clinical Periodontology 30, 954-960
135Kobayashi, T. et al. (2000) The Fcgamma receptor genotype as a risk factor for generalized early-onset periodontitis in Japanese patients. Journal of Periodontology 71, 1425-1432
136Yasuda, K. et al. (2003) FcgammaRIIB gene polymorphisms in Japanese periodontitis patients. Genes and Immunity 4, 541-546
137Sanz, M. et al. (2000) Differences in the composition of the subgingival microbiota of two periodontitis populations of different geographical origin. A comparison between Spain and The Netherlands. European Journal of Oral Sciences 108, 383-392
138McGregor, I.A. (1964) The passive transfer of human malarial immunity. American Journal of Tropical Medicine and Hygiene 13 (Suppl) 237-239
139Taylor, R.R. et al. (1998) IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. American Journal of Tropical Medicine and Hygiene 58, 406-413
140Ndungu, F.M. et al. (2002) Naturally acquired immunoglobulin (Ig)G subclass antibodies to crude asexual Plasmodium falciparum lysates: evidence for association with protection for IgG1 and disease for IgG2. Parasite Immunology 24, 77-82
141Shi, Y.P. et al. (2001) Fcgamma receptor IIa (CD32) polymorphism is associated with protection of infants against high-density Plasmodium falciparum infection. VII. Asembo Bay Cohort Project. Journal of Infectious Diseases 184, 107-111
142Cooke, G.S. et al. (2003) Association of Fcgamma receptor IIa (CD32) polymorphism with severe malaria in West Africa. American Journal of Tropical Medicine and Hygiene 69, 565-568
143Omi, K. et al. (2002) Fcgamma receptor IIA and IIIB polymorphisms are associated with susceptibility to cerebral malaria. Parasitology International 51, 361-366
144Ouma, C. et al. (2006) Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children. American Journal of Tropical Medicine and Hygiene 74, 573-577
145Nasr, A. et al. (2007) Fc gamma receptor IIa (CD32) polymorphism and antibody responses to asexual blood-stage antigens of Plasmodium falciparum malaria in Sudanese patients. Scandinavian Journal of Immunology 66, 87-96
146Nasr, A. et al. (2008) Interethnic differences in carriage of haemoglobin AS and Fcgamma receptor IIa (CD32) genotypes in children living in eastern Sudan. Acta Tropica 105, 191-195
147Sinha, S. et al. (2008) Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population. Malaria Journal 7, 13
148Omi, K. et al. (2002) Absence of association between the Fc gamma receptor IIIA-176F/V polymorphism and the severity of malaria in Thai. Japanese Journal of Infectious Diseases 55, 167-169
149Scharf, O. et al. (2001) Immunoglobulin G3 from polyclonal human immunodeficiency virus (HIV) immune globulin is more potent than other subclasses in neutralizing HIV type 1. Journal of Virology 75, 6558-6565
150Takeda, A., Tuazon, C.U. and Ennis, F.A. (1988) Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science 242, 580-583
151Tsitsikov, E.N. et al. (1995) Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat-driven transcription in human monocytes. International Immunology 7, 1665-1670
152Forthal, D.N. et al. (2007) FcgammaRIIa genotype predicts progression of HIV infection. Journal of Immunology 179, 7916-7923
153Brouwer, K.C. et al. (2004) Polymorphism of Fc receptor IIa for IgG in infants is associated with susceptibility to perinatal HIV-1 infection. AIDS 18, 1187-1194
154Schalling, M. et al. (1995) A role for a new herpes virus (KSHV) in different forms of Kaposi's sarcoma. Nature Medicine 1, 707-708
155Jawahar, S. et al. (1996) Natural killer (NK) cell deficiency associated with an epitope-deficient Fc receptor type IIIA (CD16-II). Clinical and Experimental Immunology 103, 408-413
156Lehrnbecher, T.L. et al. (2000) Variant genotypes of FcgammaRIIIA influence the development of Kaposi's sarcoma in HIV-infected men. Blood 95, 2386-2390
157Halstead, S.B. (1988) Pathogenesis of dengue: challenges to molecular biology. Science 239, 476-481
158Burke, D.S. et al. (1988) A prospective study of dengue infections in Bangkok. American Journal of Tropical Medicine and Hygiene 38, 172-180
159Kliks, S.C. et al. (1988) Evidence that maternal dengue antibodies are important in the development of dengue hemorrhagic fever in infants. American Journal of Tropical Medicine and Hygiene 38, 411-419
160Thein, S. et al. (1997) Risk factors in dengue shock syndrome. American Journal of Tropical Medicine and Hygiene 56, 566-572
161Littaua, R., Kurane, I. and Ennis, F.A. (1990) Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. Journal of Immunology 144, 3183-3186
162Loke, H. et al. (2002) Susceptibility to dengue hemorrhagic fever in vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes. American Journal of Tropical Medicine and Hygiene 67, 102-106
163Blondel, B. et al. (1998) Molecular aspects of poliovirus biology with a special focus on the interactions with nerve cells. Journal of Neurovirology 4, 1-26
164Arita, M., Horie, H. and Nomoto, A. (1999) Interaction of poliovirus with its receptor affords a high level of infectivity to the virion in poliovirus infections mediated by the Fc receptor. Journal of Virology 73, 1066-1074
165Ulvestad, E. et al. (1994) Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG. Journal of the Neurological Sciences 121, 125-131
166Beck, O.E. (1981) Distribution of virus antibody activity among human IgG subclasses. Clinical and Experimental Immunology 43, 626-632
167Rekand, T. et al. (2002) Fcgamma receptor IIIA polymorphism as a risk factor for acute poliomyelitis. Journal of Infectious Diseases 186, 1840-1843
168Starzl, T.E. et al. (1967) The clinical use of antilymphocyte globulin in renal homotransplantation. Transplantation 5 (Suppl), 1100-1105
169Wong, M. et al. (2008) TNFalpha blockade in human diseases: mechanisms and future directions. Clinical Immunology 126, 121-136
170Vose, J.M. et al. (2000) Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. Journal of Clinical Oncology 18, 1316-1323
171Suntharalingam, G. et al. (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. New England Journal of Medicine 355, 1018-1028
172Grillo-Lopez, A.J. et al. (1999) Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma. Seminars in Oncology 26, 66-73
173Looney, R.J. (2005) B cells as a therapeutic target in autoimmune diseases other than rheumatoid arthritis. Rheumatology (Oxford) 44 (Suppl 2), ii13-ii17
174Clynes, R.A. et al. (2000) Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Medicine 6, 443-446
175Zhang, Z. et al. (2003) Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507. Blood 102, 284-288
176Uchida, J. et al. (2004) The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. Journal of Experimental Medicine 199, 1659-1669
177Cartron, G. et al. (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99, 754-758
178Weng, W.K. and Levy, R. (2003) Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. Journal of Clinical Oncology 21, 3940-3947
179Kalergis, A.M. and Ravetch, J.V. (2002) Inducing tumor immunity through the selective engagement of activating Fcgamma receptors on dendritic cells. Journal of Experimental Medicine 195, 1653-1659
180Dhodapkar, K.M. et al. (2005) Selective blockade of inhibitory Fcgamma receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells. Proceedings of the National Academy of Sciences of the United States of America 102, 2910-2915
181Shields, R.L. et al. (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. Journal of Biological Chemistry 276, 6591-6604
182Lazar, G.A. et al. (2006) Engineered antibody Fc variants with enhanced effector function. Proceedings of the National Academy of Sciences of the United States of America 103, 4005-4010
183Story, C.M., Mikulska, J.E. and Simister, N.E. (1994) A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus. Journal of Experimental Medicine 180, 2377-2381
184Ghetie, V. and Ward, E.S. (2000) Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annual Review of Immunology 18, 739-766
185Molica, S. et al. (1996) Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia. Results of a crossover study. Haematologica 81, 121-126
186Basta, M. et al. (2003) F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins. Nature Medicine 9, 431-438
187Debre, M. et al. (1993) Infusion of Fc gamma fragments for treatment of children with acute immune thrombocytopenic purpura. Lancet 342, 945-949
188Bruhns, P. et al. (2003) Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease. Immunity 18, 573-581
189Samuelsson, A., Towers, T.L. and Ravetch, J.V. (2001) Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291, 484-486
190Teeling, J.L. et al. (2001) Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia. Blood 98, 1095-1099
191van Mirre, E. et al. (2004) Monomeric IgG in intravenous Ig preparations is a functional antagonist of FcgammaRII and FcgammaRIIIb. Journal of Immunology 173, 332-339
192Park-Min, K.H. et al. (2007) FcgammaRIII-dependent inhibition of interferon-gamma responses mediates suppressive effects of intravenous immune globulin. Immunity 26, 67-78
193Kaneko, Y. et al. (2006) Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors. Journal of Experimental Medicine 203, 789-797
194Abe, J. et al. (2005) Gene expression profiling of the effect of high-dose intravenous Ig in patients with Kawasaki disease. Journal of Immunology 174, 5837-5845
195Crow, A.R. et al. (2003) IVIg-mediated amelioration of murine ITP via FcgammaRIIB is independent of SHIP1, SHP-1, and Btk activity. Blood 102, 558-560
196Kaneko, Y., Nimmerjahn, F. and Ravetch, J.V. (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313, 670-673
197Anthony, R.M. et al. (2008) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proceedings of the National Academy of Sciences of the United States of America 105, 19571-19578
198Anthony, R.M. et al. (2008) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320, 373-376
199Hansen, R.J. and Balthasar, J.P. (2002) Effects of intravenous immunoglobulin on platelet count and antiplatelet antibody disposition in a rat model of immune thrombocytopenia. Blood 100, 2087-2093
200Akilesh, S. et al. (2004) The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease. Journal of Clinical Investigation 113, 1328-1333
201Wu, J. et al. (1997) A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. Journal of Clinical Investigation 100, 1059-1070
202Koene, H.R. et al. (1998) The Fc gammaRIIIA-158F allele is a risk factor for systemic lupus erythematosus. Arthritis and Rheumatism 41, 1813-1818
203Seligman, V.A. et al. (2001) The Fcgamma receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians. Arthritis and Rheumatism 44, 618-625
204Manger, K. et al. (2002) Fcgamma receptor IIa, IIIa and IIIb polymorphisms in German patients with systemic lupus erythematosus: association with clinical symptoms. Annals of the Rheumatic Diseases 61, 786-792
205Zuniga, R. et al. (2001) Low-binding alleles of Fcgamma receptor types IIA and IIIA are inherited independently and are associated with systemic lupus erythematosus in Hispanic patients. Arthritis and Rheumatism 44, 361-367
206Yun, H.R. et al. (2001) FcgammaRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients. Lupus 10, 466-472
207Lee, H.S. et al. (2003) Independent association of HLA-DR and FCgamma receptor polymorphisms in Korean patients with systemic lupus erythematosus. Rheumatology (Oxford) 42, 1501-1507
208Lee, E.B. et al. (2002) Fcgamma receptor IIIA polymorphism in Korean patients with systemic lupus erythematosus. Rheumatology International 21, 222-226
209Edberg, J.C. et al. (2002) Genetic linkage and association of Fcgamma receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus. Arthritis and Rheumatism 46, 2132-2140
210Morgan, A.W. et al. (2003) FcgammaRIIIA-158V and rheumatoid arthritis: a confirmation study. Rheumatology (Oxford) 42, 528-533
211Brun, J.G., Madland, T.M. and Vedeler, C.A. (2002) Immunoglobulin G fc-receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms related to disease severity in rheumatoid arthritis. Journal of Rheumatology 29, 1135-1140
212Morgan, A.W. et al. (2000) Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups. Arthritis and Rheumatism 43, 2328-2334
213Radstake, T.R. et al. (2003) Role of Fcgamma receptors IIA, IIIA, and IIIB in susceptibility to rheumatoid arthritis. Journal of Rheumatology 30, 926-933
214Morgan, A.W. et al. (2006) Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B. Arthritis Research and Therapy 8, R5
215Nieto, A. et al. (2000) Involvement of Fcgamma receptor IIIA genotypes in susceptibility to rheumatoid arthritis. Arthritis and Rheumatism 43, 735-739
216Milicic, A. et al. (2002) The F158V polymorphism in FcgammaRIIIA shows disparate associations with rheumatoid arthritis in two genetically distinct populations. Annals of the Rheumatic Diseases 61, 1021-1023
217Alizadeh, B.Z. et al. (2007) Association analysis of functional variants of the FcgRIIa and FcgRIIIa genes with type 1 diabetes, celiac disease and rheumatoid arthritis. Human Molecular Genetics 16, 2552-2559
218Breunis, W.B. et al. (2009) Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B. Human Mutation 30, E640-E650
Nakamura, A., Akiyama, K. and Takai, T. (2005) Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer. Expert Opinion on Therapeutic Targets 9, 169-190
Nimmerjahn, F. and Ravetch, J.V. (2007) Antibodies, Fc receptors and cancer. Current Opinion in Immunology 19, 239-245
Elkon, K. and Casali, P. (2008) Nature and functions of autoantibodies. Nature Clinical Practice Rheumatology 4, 491-498
Nimmerjahn, F. and Ravetch, J.V. (2008) Anti-inflammatory actions of intravenous immunoglobulin. Annual Review of Immunology 26, 513-533

This homepage for immunologists in Cambridge, UK, gives details of research groups in Cambridge and future immunology meetings:

Low-affinity Fcγ receptors, autoimmunity and infection

  • Lisa C. Willcocks (a1), Kenneth G.C. Smith (a1) and Menna R. Clatworthy (a1)


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