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How the Immune System Recognizes Self and Nonself pp 173–198Cite as

Fc Receptors

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Abstract

An immune response is characterized by a delicate balance; strong enough to eliminate foreign pathogens but at the same time well controlled and highly specific to prevent destruction of self-tissues. Antibodies are essential to defend the body against invading microorganisms and antibodies bound to their respective antigen in the form of immune complexes (IC) have long been recognized to be potent inflammatory stimuli. The existence of cellular receptors for antibodies was anticipated as early as 1960 (Boyden and Sorkin 1960). Starting with the molecular cloning of cellular receptors for IgG and IgE, subsequently Fc receptors (FcR) for all antibody isotypes (IgM, IgA, IgD, IgE, and IgG) have been identified (Ravetch 2003). Fc receptors are widely expressed throughout the hematopoietic system and are essential regulators of immune cell activation. By recognizing the Fc portion of antibodies in immune complexes, Fc receptors link ancestral pathways of innate immunity to the specificity of the adaptive immune system. Their cellular expression pattern on myeloid effector cells, mast cells and B cells predicted their involvement in different types of inflammatory responses, allergy and B-cell regulation. Indeed, effector mechanisms shown to be triggered by FcR crosslinking include antibody dependent cellular cytotoxicity (ADCC), phagocytosis, release of inflammatory mediators and antigen presentation (Ravetch 2003). Moreover, the potent immunoregulatory functions of ICs (consisting of IgG or IgM antibodies), ranging from a strong enhancement to complete suppression of antibody responses in addition to their more overt role as effector molecules for the elimination of foreign antigens, can now be ascribed to specific FcRs (Heyman 2000).

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References

  • Barnes N, Gavin AL, Tan PS, Mottram P, Koentgen F, Hogarth PM (2002) FcgammaRI-deficient mice show multiple alterations to inflammatory and immune responses. Immunity 16:379–389

    Article  PubMed  CAS  Google Scholar 

  • Bergtold A, Desai DD, Gavhane A, Clynes R (2005) Cell surface recycling of internalized antigen permits dendritic cell priming of B cells. Immunity 23:503–514

    Article  PubMed  CAS  Google Scholar 

  • 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 117:220–227

    Article  PubMed  CAS  Google Scholar 

  • Bolland S, Ravetch JV (2000) Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 13:277–285

    Article  PubMed  CAS  Google Scholar 

  • Bolland S, Yim YS, Tus K, Wakeland EK, Ravetch JV (2002) Genetic modifiers of systemic lupus erythematosus in FcgammaRIIB(—/—) mice. J Exp Med 195:1167–1174

    Article  PubMed  CAS  Google Scholar 

  • Bona CA, Stevenson FK (2004) B cells producing pathogenic autoantibodies. In: Honjo T, Alt FW, Neuberger MS (eds) Molecular biology of B cells. Elsevier, Boston, pp 381–402

    Google Scholar 

  • 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 115:2914–2923

    Article  PubMed  CAS  Google Scholar 

  • Boyden SV, Sorkin E (1960) The adsorption of antigen by spleen cells previously treated with antiserum in vitro. Immunology 3:272–283

    PubMed  CAS  Google Scholar 

  • Bruhns P, Samuelsson A, Pollard JW, Ravetch JV (2003) Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease. Immunity 18:573–581

    Article  PubMed  CAS  Google Scholar 

  • 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 FcgammaRIIIa gene. Blood 99:754–758

    Article  PubMed  CAS  Google Scholar 

  • Chu ZT, Tsuchiya N, Kyogoku C, Ohashi J, Qian YP, Xu SB, Mao CZ, Chu JY, Tokunaga K (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

    Article  PubMed  CAS  Google Scholar 

  • Clynes R, Calvani N, Croker BP, Richards HB (2005) Modulation of the immune response in pristane-induced lupus by expression of activation and inhibitory Fc receptors. Clin Exp Immunol 141:230–237

    Article  PubMed  CAS  Google Scholar 

  • Clynes R, Ravetch JV (1995) Cytotoxic antibodies trigger inflammation through Fc receptors. Immunity 3:21–26

    Article  PubMed  CAS  Google Scholar 

  • Clynes RA, Towers TL, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443–446

    Article  PubMed  CAS  Google Scholar 

  • Coffman RL, Savelkoul HF, Lebman DA (1989) Cytokine regulation of immunoglobulin isotype switching and expression. Semin Immunol 1:55–63

    PubMed  CAS  Google Scholar 

  • Coutelier JP, van der Logt JT, Heessen FW, Warnier G, Van Snick J (1987) IgG2a restriction of murine antibodies elicited by viral infections. J Exp Med 165:64–69

    Article  PubMed  CAS  Google Scholar 

  • Davis RS, Dennis G, Jr., Odom MR, Gibson AW, Kimberly RP, Burrows PD, Cooper MD (2002) Fc receptor homologs: newest members of a remarkably diverse Fc receptor gene family. Immunol Rev 190:123–136

    Article  PubMed  CAS  Google Scholar 

  • Davis RS, Ehrhardt GR, Leu CM, Hirano M, Cooper MD (2005) An extended family of Fc receptor relatives. Eur J Immunol 35:674–680

    Article  PubMed  CAS  Google Scholar 

  • Delamarre L, Pack M, Chang H, Mellman I, Trombetta ES (2005) Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 307:1630–1634

    Article  PubMed  CAS  Google Scholar 

  • Dhodapkar KM, Krasovsky J, Williamson B, Dhodapkar MV (2002) Antitumor monoclonal antibodies enhance cross-presentation of Cellular antigens and the generation of myelomaspecific killer T cells by dendritic cells. J Exp Med 195:125–133

    Article  PubMed  CAS  Google Scholar 

  • Dhodapkar KM, Kaufman JL, Ehlers M, Banerjee DK, Bonvini E, Koenig S, Steinman RM, Ravetch JV, Dhodapkar MV (2005) Selective blockade of inhibitory Fcgamma receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibodycoated tumor cells. Proc Natl Acad Sci USA 102:2910–2915

    Article  PubMed  CAS  Google Scholar 

  • Dijstelbloem HM, van de Winkel JG, Kallenberg CG (2001) Inflammation in autoimmunity: receptors for IgG revisited. Trends Immunol 22:510–516

    Article  PubMed  CAS  Google Scholar 

  • Dombrowicz D, Lin S, Flamand V, Brini AT, Koller BH, Kinet JP (1998) Allergy-associated FcRbeta is a molecular amplifier of IgE-and IgG-mediated in vivo responses. Immunity 8:517–529

    Article  PubMed  CAS  Google Scholar 

  • Donnadieu E, Jouvin MH, Rana S, Moffatt MF, Mockford EH, Cookson WO, Kinet JP (2003) Competing functions encoded in the allergy-associated F(c)epsilonRIbeta gene. Immunity 18:665–674

    Article  PubMed  CAS  Google Scholar 

  • Duncan AR, Winter G (1988) The binding site for C1q on IgG. Nature 332:738–740

    Article  PubMed  CAS  Google Scholar 

  • Finkelman FD, Holmes J, Katona IM, Urban JF, Jr., Beckmann MP, Park LS, Schooley KA, Coffman RL, Mosmann TR, Paul WE (1990) Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8:303–333

    Article  PubMed  CAS  Google Scholar 

  • 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 FcgammaRIIb polymorphism through exclusion from lipid rafts. Nat Med 11:1056–1058

    Article  PubMed  CAS  Google Scholar 

  • Fossati-Jimack L, Ioan-Facsinay A, Reininger L, Chicheportiche Y, Watanabe N, Saito T, Hofhuis FM, Gessner JE, Schiller C, Schmidt RE, et al (2000) Markedly different pathogenicity of four immunoglobulin G isotype-switch variants of an antierythrocyte autoantibody is based on their capacity to interact in vivo with the low-affinity Fcgamma receptor III. J Exp Med 191:1293–1302

    Article  PubMed  CAS  Google Scholar 

  • Fujii T, Hamano Y, Ueda S, Akikusa B, Yamasaki S, Ogawa M, Saisho H, Verbeek JS, Taki S, Saito T (2003) Predominant role of FcgammaRIII in the induction of accelerated nephrotoxic glomerulonephritis. Kidney Int 64:1406–1416

    Article  PubMed  CAS  Google Scholar 

  • Fukuyama H, Nimmerjahn F, Ravetch JV (2005) The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells. Nat Immunol 6:99–106

    Article  PubMed  CAS  Google Scholar 

  • Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M (2005) Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 23:749–78

    Article  PubMed  CAS  Google Scholar 

  • Gillespie SR, DeMartino RR, Zhu J, Chong HJ, Ramirez C, Shelburne CP, Bouton LA, Bailey DP, Gharse A, Mirmonsef P, et al (2004) IL-10 inhibits Fc epsilon RI expression in mouse mast cells. J Immunol 172:3181–3188

    PubMed  CAS  Google Scholar 

  • Goodnow CC, Sprent J, de St Groth BF, Vinuesa CG (2005) Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435:590–597

    Article  PubMed  CAS  Google Scholar 

  • Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, Fear D, Smurthwaite L (2003) The biology of IGE and the basis of allergic disease. Annu Rev Immunol 21:579–628

    Article  PubMed  CAS  Google Scholar 

  • Grimaldi CM, Hicks R, Diamond B (2005) B-cell selection and susceptibility to autoimmunity. J Immunol 174:1775–1781

    PubMed  CAS  Google Scholar 

  • Groh V, Li YQ, Cioca D, Hunder NN, Wang W, Riddell SR, Yee C, Spies T (2005) Efficient cross-priming of tumor antigen-specific T cells by dendritic cells sensitized with diverse anti-MICA opsonized tumor cells. Proc Natl Acad Sci USA 102:6461–6466

    Article  PubMed  CAS  Google Scholar 

  • Gulle H, Samstag A, Eibl MM, Wolf HM (1998) Physical and functional association of Fc alpha R with protein tyrosine kinase Lyn. Blood 91:383–391

    PubMed  CAS  Google Scholar 

  • Guyre PM, Morganelli PM, Miller R (1983) Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest 72: 393–397

    Article  PubMed  CAS  Google Scholar 

  • Hamaguchi Y, Xiu Y, Komura K, Nimmerjahn F, Tedder TF (2006) Antibody isotype-specificengagement of Fc gamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. J Exp Med 203:743–753

    Article  PubMed  CAS  Google Scholar 

  • Hazenbos WL, Gessner JE, Hofhuis FM, Kuipers H, Meyer D, Heijnen IA, Schmidt RE, Sandor M, Capel PJ, Daeron M, et al (1996) Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Immunity 5:181–188

    Article  PubMed  CAS  Google Scholar 

  • Heyman B (2000) Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu Rev Immunol 18:709–737

    Article  PubMed  CAS  Google Scholar 

  • Heyman B (2002) IgE-mediated enhancement of antibody responses: the beneficial function of IgE? Allergy 57:577–585

    Article  PubMed  CAS  Google Scholar 

  • Hulett MD, Hogarth PM (1994) Molecular basis of Fc receptor function. Adv Immunol 57:1–127

    PubMed  CAS  Google Scholar 

  • Ioan-Facsinay A, de Kimpe SJ, Hellwig SM, van Lent PL, Hofhuis FM, van Ojik HH, Sedlik C, da Silveira SA, Gerber J, de Jong YF, et al (2002) FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection. Immunity 16:391–402

    Article  PubMed  CAS  Google Scholar 

  • Ji H, Ohmura K, Mahmood U, Lee DM, Hofhuis FM, Boackle SA, Takahashi K, Holers VM, Walport M, Gerard C, et al (2002) Arthritis critically dependent on innate immune system players. Immunity 16:157–168

    Article  PubMed  CAS  Google Scholar 

  • Jiang Y, Hirose S, Sanokawa-Akakura R, Abe M, Mi X, Li N, Miura Y, Shirai J, Zhang D, Hamano Y, Shirai T (1999) Genetically determined aberrant down-regulation of FcgammaRIIB1 in germinal center B cells associated with hyper-IgG and IgG autoantibodies in murine systemic lupus erythematosus. Int Immunol 11:1685–1691

    Article  PubMed  CAS  Google Scholar 

  • Jiang Y, Hirose S, Abe M, Sanokawa-Akakura R, Ohtsuji M, Mi X, Li N, Xiu Y, Zhang D, Shirai J, et al (2000) Polymorphisms in IgG Fc receptor IIB regulatory regions associated with autoimmune susceptibility. Immunogenetics 51:429–435

    Article  PubMed  CAS  Google Scholar 

  • Kalergis AM, Ravetch JV (2002) Inducing tumor immunity through the selective engagement of activating Fcgamma receptors on dendritic cells. J Exp Med 195:1653–1659

    Article  PubMed  CAS  Google Scholar 

  • Kaneko Y, Nimmerjahn F, Madaio M, Ravetch JV (2006) Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific FcRs. J Exp Med 203:789–797

    Article  PubMed  CAS  Google Scholar 

  • Kipps TJ, Parham P, Punt J, Herzenberg LA (1985) Importance of immunoglobulin isotype in human antibody-dependent, cell-mediated cytotoxicity directed by murine monoclonal antibodies. J Exp Med 161:1–17

    Article  PubMed  CAS  Google Scholar 

  • Kono H, Kyogoku C, Suzuki T, Tsuchiya N, Honda H, Yamamoto K, Tokunaga K, Honda Z (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. Hum Mol Genet 14:2881–2892

    Article  PubMed  CAS  Google Scholar 

  • Kraft S, Novak N (2005) Fc receptors as determinants of allergic reactions. Trends Immunol 27:88–95

    Article  PubMed  CAS  Google Scholar 

  • Kushnir N, Liu L, MacPherson GG (1998) Dendritic cells and resting B cells form clusters in vitro and in vivo: T-cell independence, partial LFA-1 dependence, and regulation by crosslinking surface molecules. J Immunol 160:1774–1781

    PubMed  CAS  Google Scholar 

  • Kyogoku C, Tsuchiya N, Wu H, Tsao BP, Tokunaga K (2004) Association of Fcgamma receptor IIA, but not IIB and IIIA, polymorphisms with systemic lupus erythematosus: A family-based association study in Caucasians. Arthritis Rheum 50:671–673

    Article  PubMed  CAS  Google Scholar 

  • Lang ML, Shen L, Wade WF (1999) Gamma-chain dependent recruitment of tyrosine kinases to membrane rafts by the human IgA receptor Fc alpha R. J Immunol 163:5391–5398

    PubMed  CAS  Google Scholar 

  • Launay P, Lehuen A, Kawakami T, Blank U, Monteiro RC (1998) IgA Fc receptor (CD89) activation enables coupling to syk and Btk tyrosine kinase pathways: differential signaling after IFN-gamma or phorbol ester stimulation. J Leukoc Biol 63:636–642

    PubMed  CAS  Google Scholar 

  • MacGlashan D Jr (2005) IgE and Fc{epsilon}RI regulation. Ann N Y Acad Sci 1050:73–88

    Article  PubMed  CAS  Google Scholar 

  • Markine-Goriaynoff D, Coutelier JP (2002) Increased efficacy of the immunoglobulin G2a subclass in antibody-mediated protection against lactate dehydrogenase-elevating virus-induced polioencephalomyelitis revealed with switch mutants. J Virol 76:432–435

    Article  PubMed  CAS  Google Scholar 

  • McGaha TL, Sorrentino B, Ravetch JV (2005) Restoration of tolerance in lupus by targeted inhibitory receptor expression. Science 307:590–593

    Article  PubMed  CAS  Google Scholar 

  • Mechetina LV, Najakshin AM, Alabyev BY, Chikaev NA, Taranin AV (2002) Identification of CD16-2, a novel mouse receptor homologous to CD16/Fc gamma RIII. Immunogenetics 54:463–468

    Article  PubMed  CAS  Google Scholar 

  • Meffre E, Casellas R, Nussenzweig MC (2000) Antibody regulation of B-cell development. Nat Immunol 1:379–385

    Article  PubMed  CAS  Google Scholar 

  • Meyer D, Schiller C, Westermann J, Izui S, Hazenbos WL, Verbeek JS, Schmidt RE, Gessner JE (1998) FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia. Blood 92:3997–4002

    PubMed  CAS  Google Scholar 

  • Monteiro RC, Van De Winkel JG (2003) IgA Fc receptors. Annu Rev Immunol 21:177–204

    Article  PubMed  CAS  Google Scholar 

  • Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  PubMed  CAS  Google Scholar 

  • Nguyen C, Limaye N, Wakeland EK (2002) Susceptibility genes in the pathogenesis of murine lupus. Arthritis Res 4:S255–263

    Article  PubMed  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2005) Divergent immunoglobulin g subclass activity through selective Fc receptor binding. Science 310:1510–1512

    Article  PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Bruhns P, Horiuchi K, Ravetch JV (2005) FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Immunity 23:41–51

    Article  PubMed  CAS  Google Scholar 

  • Nishimura H, Nose M, Hiai H, Minato N, Honjo T (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:141–151

    Article  PubMed  CAS  Google Scholar 

  • Novak N, Kraft S, Bieber T (2001) IgE receptors. Curr Opin Immunol 13:721–726

    Article  PubMed  CAS  Google Scholar 

  • Okayama Y, Kirshenbaum AS, Metcalfe DD (2000) Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma. J Immunol 164:4332–4339

    PubMed  CAS  Google Scholar 

  • Okazaki T, Otaka Y, Wang J, Hiai H, Takai T, Ravetch JV, Honjo T (2005) Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/-mice. J Exp Med 202:1643–1648

    Article  PubMed  CAS  Google Scholar 

  • O’Keefe TL, Williams GT, Batista FD, Neuberger MS (1999) Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies. J Exp Med 189:1307–1313

    Article  PubMed  CAS  Google Scholar 

  • Otten MA, van Egmond M (2004) The Fc receptor for IgA (FcalphaRI, CD89). Immunol Lett 92:23–31

    Article  PubMed  CAS  Google Scholar 

  • Park SY, Ueda S, Ohno H, Hamano Y, Tanaka M, Shiratori T, Yamazaki T, Arase H, Arase N, Karasawa A, et al (1998) Resistance of Fc receptor-deficient mice to fatal glomerulonephritis. J Clin Invest 102:1229–1238

    Article  PubMed  CAS  Google Scholar 

  • Park RK, Izadi KD, Deo YM, Durden DL (1999) Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling. Blood 94:2112–2120

    PubMed  CAS  Google Scholar 

  • Pearse RN, Kawabe T, Bolland S, Guinamard R, Kurosaki T, Ravetch JV (1999) SHIP recruitment attenuates Fc gamma RIIB-induced B-cell apoptosis. Immunity 10:753–760

    Article  PubMed  CAS  Google Scholar 

  • Penninger JM, Timms E, Shahinian A, Jezo-Bremond A, Nishina H, Ionescu J, Hedrick SM, Mak TW (1995) Alloreactive gamma delta thymocytes utilize distinct costimulatory signals from peripheral T cells. J Immunol 155:3847–3855

    PubMed  CAS  Google Scholar 

  • Pricop L, Redecha P, Teillaud JL, Frey J, Fridman WH, Sautes-Fridman C, Salmon JE (2001) Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines. J Immunol 166:531–537

    PubMed  CAS  Google Scholar 

  • Pritchard NR, Cutler AJ, Uribe S, Chadban SJ, Morley BJ, Smith KG (2000) Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcgammaRII. Curr Biol 10:227–230

    Article  PubMed  CAS  Google Scholar 

  • Qiu WQ, de Bruin D, Brownstein BH, Pearse R, Ravetch JV (1990) Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science 248:732–735

    Article  PubMed  CAS  Google Scholar 

  • Radeke HH, Janssen-Graalfs I, Sowa EN, Chouchakova N, Skokowa J, Loscher F, Schmidt RE, Heeringa P, Gessner JE (2002) Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis. J Biol Chem 277:27535–27544

    Article  PubMed  CAS  Google Scholar 

  • Rafiq K, Bergtold A, Clynes R (2002) Immune complex-mediated antigen presentation induces tumor immunity. J Clin Invest 110:71–79

    PubMed  CAS  Google Scholar 

  • Ravetch JV (2003) Fc receptors. In: Paul WE (ed) Fundamental immunology. Lippincott-Raven, Philadelphia, pp 685–700

    Google Scholar 

  • Ravetch JV, Bolland S (2001) IgG Fc receptors. Annu Rev Immunol 19:275–290

    Article  PubMed  CAS  Google Scholar 

  • Ravetch JV, Clynes RA (1998) Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16:421–432

    Article  PubMed  CAS  Google Scholar 

  • Ravetch JV, Kinet JP (1991) Fc receptors. Annu Rev Immunol 9:457–492

    PubMed  CAS  Google Scholar 

  • Ravetch JV, Lanier LL (2000) Immune inhibitory receptors. Science 290:84–89

    Article  PubMed  CAS  Google Scholar 

  • Ray SK, Putterman C, Diamond B (1996) Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease. Proc Natl Acad Sci USA 93:2019–2024

    Article  PubMed  CAS  Google Scholar 

  • Regnault A, Lankar D, Lacabanne V, Rodriguez A, Thery C, Rescigno M, Saito T, Verbeek S, Bonnerot C, Ricciardi-Castagnoli P, Amigorena S (1999) Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 189:371–380

    Article  PubMed  CAS  Google Scholar 

  • Rudge EU, Cutler AJ, Pritchard NR, Smith KG (2002) Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes CD22 and Fc gamma RII-mediated B-cell suppression. J Exp Med 195:1079–1085

    Article  PubMed  CAS  Google Scholar 

  • Samsom JN, van Berkel LA, van Helvoort JM, Unger WW, Jansen W, Thepen T, Mebius RE, Verbeek SS, Kraal G (2005) Fc gamma RIIB regulates nasal and oral tolerance: a role for dendritic cells. J Immunol 174:5279–5287

    PubMed  CAS  Google Scholar 

  • Samuelsson A, Towers TL, Ravetch JV (2001) Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291:484–486

    Article  PubMed  CAS  Google Scholar 

  • Schlageter AM, Kozel TR (1990) Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. Infect Immun 58:1914–1918

    PubMed  CAS  Google Scholar 

  • Shibuya A, Sakamoto N, Shimizu Y, Shibuya K, Osawa M, Hiroyama T, Eyre HJ, Sutherland GR, Endo Y, Fujita T, et al (2000) Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes. Nat Immunol 1:441–446

    Article  PubMed  CAS  Google Scholar 

  • Shushakova N, Skokowa J, Schulman J, Baumann U, Zwirner J, Schmidt RE, Gessner JE (2002) C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease. J Clin Invest 110:1823–1830

    PubMed  CAS  Google Scholar 

  • Siriboonrit U, Tsuchiya N, Sirikong M, Kyogoku C, Bejrachandra S, Suthipinittharm P, Luangtrakool K, Srinak D, Thongpradit R, Fujiwara K, et al (2003) Association of Fcgamma receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 61:374–383

    Article  PubMed  CAS  Google Scholar 

  • Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K, Iyoda T, Ravetch J, Dhodapkar M, Inaba K, Nussenzweig M (2003) Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann N Y Acad Sci 987:15–25

    Article  PubMed  CAS  Google Scholar 

  • Sylvestre DL, Ravetch JV (1994) Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade. Science 265:1095–1098

    Article  PubMed  CAS  Google Scholar 

  • Taborda CP, Rivera J, Zaragoza O, Casadevall A (2003) More is not necessarily better: prozonelike effects in passive immunization with IgG. J Immunol 170:3621–3630

    PubMed  CAS  Google Scholar 

  • Takai T (2002) Roles of Fc receptors in autoimmunity. Nat Rev Immunol 2:580–592

    PubMed  CAS  Google Scholar 

  • Takai T, Li M, Sylvestre D, Clynes R, Ravetch JV (1994) FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 76:519–529

    Article  PubMed  CAS  Google Scholar 

  • Takai T, Ono M, Hikida M, Ohmori H, Ravetch JV (1996) Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. Nature 379:346–349

    Article  PubMed  CAS  Google Scholar 

  • Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH, Penninger JM, Timms E, Shahinian A, Jezo-Bremond A, et al (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3:541–547

    Article  PubMed  CAS  Google Scholar 

  • Torigoe C, Inman JK, Metzger H (1998) An unusual mechanism for ligand antagonism. Science 281:568–572

    Article  PubMed  CAS  Google Scholar 

  • Tridandapani S, Wardrop R, Baran CP, Wang Y, Opalek JM, Caligiuri MA, Marsh CB (2003) TGF-beta 1 supresses myeloid Fc gamma receptor function by regulating the expression and function of the common gamma-subunit. J Immunol 170:4572–4577

    PubMed  CAS  Google Scholar 

  • Tzeng SJ, Bolland S, Inabe K, Kurosaki T, Pierce SK (2005) The B-cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl-family kinase dependent pathway. J Biol Chem 280:35247–35254

    Article  PubMed  CAS  Google Scholar 

  • 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 199:1659–1669

    Article  PubMed  CAS  Google Scholar 

  • Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC (2003) Predominant autoantibody production by early human B-cell precursors. Science 301:1374–1377

    Article  PubMed  CAS  Google Scholar 

  • Watanabe T, Okano M, Hattori H, Yoshino T, Ohno N, Ohta N, Sugata Y, Orita Y, Takai T, Nishizaki K (2004) Roles of FcgammaRIIB in nasal eosinophilia and IgE production in murine allergic rhinitis. Am J Respir Crit Care Med 169:105–112

    Article  PubMed  Google Scholar 

  • Weng WK, Levy R (2003) Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 21:3940–3947

    Article  PubMed  CAS  Google Scholar 

  • Weng WK, Czerwinski D, Timmerman J, Hsu FJ, Levy R (2004) Clinical outcome of lymphoma patients after idiotype vaccination is correlated with humoral immune response and immunoglobulin G Fc receptor genotype. J Clin Oncol 22:4717–4724

    Article  PubMed  CAS  Google Scholar 

  • Wykes M, Pombo A, Jenkins C, MacPherson GG (1998) Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response. J Immunol 161:1313–1319

    PubMed  CAS  Google Scholar 

  • Xiu Y, Nakamura K, Abe M, Li N, Wen XS, Jiang Y, Zhang D, Tsurui H, Matsuoka S, Hamano Y, et al (2002) Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses. J Immunol 169:4340–4346

    PubMed  CAS  Google Scholar 

  • Zhang M, Zhang Z, Garmestani K, Goldman CK, Ravetch JV, Brechbiel MW, Carrasquillo JA, Waldmann TA (2004) Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult T-cell leukemia. Cancer Res 64:5825–5829

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Molecular Genetics and Immunology, Rockefeller University, 1230 York Avenue, New York, NY, 10021, USA

    Falk Nimmerjahn & Jeffrey V. Ravetch

  2. Laboratory of Experimental Immunology and Immunotherapy, University of Erlangen-Nuernberg, Nikolaus-Fiebiger-Center for Molecular Medicine, Glueckstrasse 6, 91054, Erlangen, Germany

    Falk Nimmerjahn

Authors
  1. Falk Nimmerjahn
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  2. Jeffrey V. Ravetch
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Editors and Affiliations

  1. Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba, 278-0022, Japan

    Daisuke Kitamura (Professor) (Professor)

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© 2008 Springer

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Nimmerjahn, F., Ravetch, J.V. (2008). Fc Receptors. In: Kitamura, D. (eds) How the Immune System Recognizes Self and Nonself. Springer, Tokyo. https://doi.org/10.1007/978-4-431-73884-8_6

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