Skip to main content
SpringerLink
Log in

FcγRs in Health and Disease

  • Chapter
  • First Online:
Negative Co-Receptors and Ligands

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 350))

Abstract

Genetic defects affecting the humoral immune response and especially the production of antibodies of the immunoglobulin G (IgG) isotype result in a heightened susceptibility to infections. Studies over the last years have demonstrated the crucial role of Fc-receptors for IgG (FcγRs) widely expressed on innate immune effector cells in mediating the protective function of IgG. During the last years, additional ligands interacting with FcγRs as well as additional receptors binding to IgG glycosylation variants have been identified. In this review, we discuss how the interaction of these different ligands with classical and novel Fcγ-receptors influences the immune response and which strategies microorganisms have developed to prevent them.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agrawal A, Singh PP, Bottazzi B, Garlanda C, Mantovani A (2009) Pattern recognition by pentraxins. Adv Exp Med Biol 653:98–116

    PubMed  CAS  Google Scholar 

  • 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 USA 105:15005–15009

    PubMed  CAS  Google Scholar 

  • Allhorn M, Collin M (2009) Sugar-free antibodies–the bacterial solution to autoimmunity? Ann NY Acad Sci 1173:664–669

    PubMed  CAS  Google Scholar 

  • Allhorn M, Olin AI, Nimmerjahn F, Collin M (2008) Human IgG/Fc gamma R interactions are modulated by streptococcal IgG glycan hydrolysis. PLoS One 3:e1413

    PubMed  Google Scholar 

  • Anderson CL, Grey HM (1974) Receptors for aggregated IgG on mouse lymphocytes: their presence on thymocytes, thymus-derived, and bone marrow-derived lymphocytes. J Exp Med 139:1175–1188

    PubMed  CAS  Google Scholar 

  • Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV (2008a) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320:373–376

    PubMed  CAS  Google Scholar 

  • Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008b) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 105:19571–19578

    PubMed  CAS  Google Scholar 

  • Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21–50

    PubMed  CAS  Google Scholar 

  • Atalay R, Zimmermann A, Wagner M, Borst E, Benz C, Messerle M, Hengel H (2002) Identification and expression of human cytomegalovirus transcription units coding for two distinct Fcgamma receptor homologs. J Virol 76:8596–8608

    PubMed  CAS  Google Scholar 

  • Azeredo da Silveira S, Kikuchi S, Fossati-Jimack L, Moll T, Saito T, Verbeek JS, Botto M, Walport MJ, Carroll M, Izui S (2002) Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 isotypes of a high affinity anti-erythrocyte autoantibody. J Exp Med 195:665–672

    PubMed  CAS  Google Scholar 

  • Baerenwaldt A, Nimmerjahn F (2008) Immune regulation – Fc gamma RIIB – regulating the balance between protective and autoreactive immune responses. Immun Cell Biol 86:482–484

    CAS  Google Scholar 

  • Ballow M (2002) Primary immunodeficiency disorders: antibody deficiency. J Allergy Clin Immunol 109:581–591

    PubMed  CAS  Google Scholar 

  • Balsitis SJ, Williams KL, Lachica R, Flores D, Kyle JL, Mehlhop E, Johnson S, Diamond MS, Beatty PR, Harris E (2010) Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. PLoS Pathog 6:e1000790

    PubMed  Google Scholar 

  • Baudino L, Nimmerjahn F, Azeredo da Silveira S, Martinez-Soria E, Saito T, Carroll M, Ravetch JV, Verbeek JS, Izui S (2008) Differential contribution of three activating IgG Fc receptors (FcgammaRI, FcgammaRIII, and FcgammaRIV) to IgG2a- and IgG2b-induced autoimmune hemolytic anemia in mice. J Immunol 180:1948–1953

    PubMed  CAS  Google Scholar 

  • Bergamaschi A, David A, Le Rouzic E, Nisole S, Barre-Sinoussi F, Pancino G (2009) The CDK inhibitor p21Cip1/WAF1 is induced by FcgammaR activation and restricts the replication of human immunodeficiency virus type 1 and related primate lentiviruses in human macrophages. J Virol 83:12253–12265

    PubMed  CAS  Google Scholar 

  • Bevaart L, Jansen MJ, van Vugt MJ, Verbeek JS, van de Winkel JG, Leusen JH (2006) The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma. Cancer Res 66:1261–1264

    PubMed  CAS  Google Scholar 

  • Bharadwaj D, Stein MP, Volzer M, Mold C, Du Clos TW (1999) The major receptor for C-reactive protein on leukocytes is fcgamma receptor II. J Exp Med 190:585–590

    PubMed  CAS  Google Scholar 

  • Bharadwaj D, Mold C, Markham E, Du Clos TW (2001) Serum amyloid P component binds to Fc gamma receptors and opsonizes particles for phagocytosis. J Immunol 166:6735–6741

    PubMed  CAS  Google Scholar 

  • Bolland S, Ravetch JV (1999) Inhibitory pathways triggered by ITIM-containing receptors. Adv Immunol 72:149–177

    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

    PubMed  CAS  Google Scholar 

  • Bond A, Cooke A, Hay FC (1990) Glycosylation of IgG, immune complexes and IgG subclasses in the MRL-lpr/lpr mouse model of rheumatoid arthritis. Eur J Immunol 20:2229–2233

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Bredius RG, Derkx BH, Fijen CA, de Wit TP, de Haas M, Weening RS, van de Winkel JG, Out TA (1994) Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children. J Infect Dis 170:848–853

    PubMed  CAS  Google Scholar 

  • Briles DE, Forman C, Hudak S, Claflin JL (1984a) The effects of idiotype on the ability of IgG1 anti-phosphorylcholine antibodies to protect mice from fatal infection with Streptococcus pneumoniae. Eur J Immunol 14:1027–1030

    PubMed  CAS  Google Scholar 

  • Briles DE, Forman C, Hudak S, Claflin JL (1984b) The effects of subclass on the ability of anti-phosphocholine antibodies to protect mice from fatal infection with Streptococcus pneumoniae. J Mol Cell Immunol 1:305–309

    PubMed  CAS  Google Scholar 

  • Brouwer KC, Lal RB, Mirel LB, Yang C, van Eijk AM, Ayisi J, Otieno J, Nahlen BL, Steketee R, Lal AA, Shi YP (2004) Polymorphism of Fc receptor IIa for IgG in infants is associated with susceptibility to perinatal HIV-1 infection. AIDS 18:1187–1194

    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

    PubMed  CAS  Google Scholar 

  • Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daeron M (2009) Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood 113:3716–3725

    PubMed  CAS  Google Scholar 

  • Carroll MC (2004) The complement system in regulation of adaptive immunity. Nat Immunol 5:981–986

    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

    PubMed  CAS  Google Scholar 

  • Clatworthy MR, Smith KG (2004) FcgammaRIIb balances efficient pathogen clearance and the cytokine-mediated consequences of sepsis. J Exp Med 199:717–723

    PubMed  CAS  Google Scholar 

  • Clatworthy MR, Willcocks L, Urban B, Langhorne J, Williams TN, Peshu N, Watkins NA, Floto RA, Smith KG (2007) Systemic lupus erythematosus-associated defects in the inhibitory receptor FcgammaRIIb reduce susceptibility to malaria. Proc Natl Acad Sci USA 104:7169–7174

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Collin M, Olsen A (2001) Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins. Infect Immun 69:7187–7189

    PubMed  CAS  Google Scholar 

  • Daeron M, Lesourne R (2006) Negative signaling in Fc receptor complexes. Adv Immunol 89:39–86

    PubMed  CAS  Google Scholar 

  • David A, Saez-Cirion A, Versmisse P, Malbec O, Iannascoli B, Herschke F, Lucas M, Barre-Sinoussi F, Mouscadet JF, Daeron M, Pancino G (2006) The engagement of activating FcgammaRs inhibits primate lentivirus replication in human macrophages. J Immunol 177:6291–6300

    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 antibody-coated tumor cells. Proc Natl Acad Sci USA 102:2910–2915

    PubMed  CAS  Google Scholar 

  • Dubin G, Socolof E, Frank I, Friedman HM (1991) Herpes simplex virus type 1 Fc receptor protects infected cells from antibody-dependent cellular cytotoxicity. J Virol 65:7046–7050

    PubMed  CAS  Google Scholar 

  • Dutertre CA, Bonnin-Gelize E, Pulford K, Bourel D, Fridman WH, Teillaud JL (2008) A novel subset of NK cells expressing high levels of inhibitory FcgammaRIIB modulating antibody-dependent function. J Leukoc Biol 84:1511–1520

    PubMed  CAS  Google Scholar 

  • Ferrara C, Stuart F, Sondermann P, Brunker P, Umana P (2006) The carbohydrate at FcgammaRIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms. J Biol Chem 281:5032–5036

    PubMed  CAS  Google Scholar 

  • Fijen CA, Bredius RG, Kuijper EJ, Out TA, De Haas M, De Wit AP, Daha MR, De Winkel JG (2000) The role of Fcgamma receptor polymorphisms and C3 in the immune defence against Neisseria meningitidis in complement-deficient individuals. Clin Exp Immunol 120:338–345

    PubMed  CAS  Google Scholar 

  • Florese RH, Van Rompay KK, Aldrich K, Forthal DN, Landucci G, Mahalanabis M, Haigwood N, Venzon D, Kalyanaraman VS, Marthas ML, Robert-Guroff M (2006) Evaluation of passively transferred, nonneutralizing antibody-dependent cellular cytotoxicity-mediating IgG in protection of neonatal rhesus macaques against oral SIVmac251 challenge. J Immunol 177:4028–4036

    PubMed  CAS  Google Scholar 

  • Forthal DN, Moog C (2009) Fc receptor-mediated antiviral antibodies. Curr Opin HIV AIDS 4:388–393

    PubMed  Google Scholar 

  • Fossati-Jimack L, Ioan-Facsinay A, Reininger L, Chicheportiche Y, Watanabe N, Saito T, Hofhuis FM, Gessner JE, Schiller C, Schmidt RE, Honjo T, Verbeek JS, Izui S (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

    PubMed  CAS  Google Scholar 

  • Frank I, Friedman HM (1989) A novel function of the herpes simplex virus type 1 Fc receptor: participation in bipolar bridging of antiviral immunoglobulin G. J Virol 63:4479–4488

    PubMed  CAS  Google Scholar 

  • Gavin AL, Tan PS, Hogarth PM (1998) Gain-of-function mutations in FcgammaRI of NOD mice: implications for the evolution of the Ig superfamily. EMBO J 17:3850–3857

    PubMed  CAS  Google Scholar 

  • Giorgini A, Brown HJ, Lock HR, Nimmerjahn F, Ravetch JV, Verbeek JS, Sacks SH, Robson MG (2008) Fc gamma RIII and Fc gamma RIV are indispensable for acute glomerular inflammation induced by switch variant monoclonal antibodies. J Immunol 181:8745–8752

    PubMed  CAS  Google Scholar 

  • Gjertsson I, Kleinau S, Tarkowski A (2002) The impact of Fcgamma receptors on Staphylococcus aureus infection. Microb Pathog 33:145–152

    PubMed  CAS  Google Scholar 

  • Gomez-Roman VR, Patterson LJ, Venzon D, Liewehr D, Aldrich K, Florese R, Robert-Guroff M (2005) Vaccine-elicited antibodies mediate antibody-dependent cellular cytotoxicity correlated with significantly reduced acute viremia in rhesus macaques challenged with SIVmac251. J Immunol 174:2185–2189

    PubMed  CAS  Google Scholar 

  • Gray CA, Lawrence RA (2002) A role for antibody and Fc receptor in the clearance of Brugia malayi microfilariae. Eur J Immunol 32:1114–1120

    PubMed  CAS  Google Scholar 

  • Hamaguchi Y, Xiu Y, Komura K, Nimmerjahn F, Tedder TF (2006) Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. J Exp Med 203:743–753, Epub 2006 Mar 6

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Hellwig SM, van Oirschot HF, Hazenbos WL, van Spriel AB, Mooi FR, van De Winkel JG (2001) Targeting to Fcgamma receptors, but not CR3 (CD11b/CD18), increases clearance of Bordetella pertussis. J Infect Dis 183:871–879

    PubMed  CAS  Google Scholar 

  • Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, Bakker JM, Lanigan CM, Landucci G, Forthal DN, Parren PW, Marx PA, Burton DR (2007) Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449:101–104

    PubMed  CAS  Google Scholar 

  • Hirano M, Davis RS, Fine WD, Nakamura S, Shimizu K, Yagi H, Kato K, Stephan RP, Cooper MD (2007) IgEb immune complexes activate macrophages through FcgammaRIV binding. Nat Immunol 8:762–771

    PubMed  CAS  Google Scholar 

  • Hogarth PM (2002) Fc receptors are major mediators of antibody based inflammation in autoimmunity. Curr Opin Immunol 14:798–802

    PubMed  CAS  Google Scholar 

  • Holl V, Hemmerter S, Burrer R, Schmidt S, Bohbot A, Aubertin AM, Moog C (2004) Involvement of Fc gamma RI (CD64) in the mechanism of HIV-1 inhibition by polyclonal IgG purified from infected patients in cultured monocyte-derived macrophages. J Immunol 173:6274–6283

    PubMed  CAS  Google Scholar 

  • Holl V, Peressin M, Decoville T, Schmidt S, Zolla-Pazner S, Aubertin AM, Moog C (2006a) Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells. J Virol 80:6177–6181

    PubMed  CAS  Google Scholar 

  • Holl V, Peressin M, Schmidt S, Decoville T, Zolla-Pazner S, Aubertin AM, Moog C (2006b) Efficient inhibition of HIV-1 replication in human immature monocyte-derived dendritic cells by purified anti-HIV-1 IgG without induction of maturation. Blood 107:4466–4474

    PubMed  CAS  Google Scholar 

  • Huber VC, Lynch JM, Bucher DJ, Le J, Metzger DW (2001) Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections. J Immunol 166:7381–7388

    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, Roozendaal R, Aarden LA, van den Berg WB, Saito T, Mosser D, Amigorena S, Izui S, van Ommen GJ, van Vugt M, van de Winkel JG, Verbeek JS (2002) FcgammaRI (CD64) contributes substantially to severity of arthritis, hypersensitivity responses, and protection from bacterial infection. Immunity 16:391–402

    PubMed  CAS  Google Scholar 

  • Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327:291–295

    PubMed  CAS  Google Scholar 

  • Jefferis R (2009) Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov 8:226–234

    PubMed  CAS  Google Scholar 

  • Johansson BP, Shannon O, Bjorck L (2008) IdeS: a bacterial proteolytic enzyme with therapeutic potential. PLoS One 3:e1692

    PubMed  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

    PubMed  CAS  Google Scholar 

  • Kaminski MS, Kitamura K, Maloney DG, Campbell MJ, Levy R (1986) Importance of antibody isotype in monoclonal anti-idiotype therapy of a murine B cell lymphoma. A study of hybridoma class switch variants. J Immunol 136:1123–1130

    PubMed  CAS  Google Scholar 

  • Kaneko Y, Nimmerjahn F, Madaio MP, Ravetch JV (2006a) Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors. J Exp Med 203:789–797, Epub 2006 Mar 6

    PubMed  CAS  Google Scholar 

  • Kaneko Y, Nimmerjahn F, Ravetch JV (2006b) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313:670–673

    PubMed  CAS  Google Scholar 

  • Karlsson Hedestam GB, Fouchier RA, Phogat S, Burton DR, Sodroski J, Wyatt RT (2008) The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Microbiol 6:143–155

    PubMed  CAS  Google Scholar 

  • Kima PE, Constant SL, Hannum L, Colmenares M, Lee KS, Haberman AM, Shlomchik MJ, McMahon-Pratt D (2000) Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis. J Exp Med 191:1063–1068

    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

    PubMed  CAS  Google Scholar 

  • Lambert SL, Okada CY, Levy R (2004) TCR vaccines against a murine T cell lymphoma: a primary role for antibodies of the IgG2c class in tumor protection. J Immunol 172:929–936

    PubMed  CAS  Google Scholar 

  • Langone JJ (1982) Protein A of Staphylococcus aureus and related immunoglobulin receptors produced by streptococci and pneumonococci. Adv Immunol 32:157–252

    PubMed  CAS  Google Scholar 

  • Leclerc JC, Plater C, Fridman WH (1977) The role of the Fc receptor (FcR) of thymus-derived lymphocytes. I. Presence of FcR on cytotoxic lymphocytes and absence of direct role in cytotoxicity. Eur J Immunol 7:543–548

    PubMed  CAS  Google Scholar 

  • Littaua R, Kurane I, Ennis FA (1990) Human IgG Fc receptor II mediates antibody-dependent enhancement of dengue virus infection. J Immunol 144:3183–3186

    PubMed  CAS  Google Scholar 

  • Loke H, Bethell D, Phuong CX, Day N, White N, Farrar J, Hill A (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. Am J Trop Med Hyg 67:102–106

    PubMed  CAS  Google Scholar 

  • Lu J, Marnell LL, Marjon KD, Mold C, Du Clos TW, Sun PD (2008) Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature 456:989–992

    PubMed  CAS  Google Scholar 

  • Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB (1995) Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med 1:237–243

    PubMed  CAS  Google Scholar 

  • Mancardi DA, Iannascoli B, Hoos S, England P, Daeron M, Bruhns P (2008) FcgammaRIV is a mouse IgE receptor that resembles macrophage FcepsilonRI in humans and promotes IgE-induced lung inflammation. J Clin Invest 118:3738–3750

    PubMed  CAS  Google Scholar 

  • Marjon KD, Marnell LL, Mold C, Du Clos TW (2009) Macrophages activated by C-reactive protein through Fc gamma RI transfer suppression of immune thrombocytopenia. J Immunol 182:1397–1403

    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

    PubMed  CAS  Google Scholar 

  • Marnell L, Mold C, Du Clos TW (2005) C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol 117:104–111

    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 

  • Mimura Y, Sondermann P, Ghirlando R, Lund J, Young SP, Goodall M, Jefferis R (2001) Role of oligosaccharide residues of IgG1-Fc in Fc gamma RIIb binding. J Biol Chem 276:45539–45547

    PubMed  CAS  Google Scholar 

  • Mizuochi T, Hamako J, Nose M, Titani K (1990) Structural changes in the oligosaccharide chains of IgG in autoimmune MRL/Mp-lpr/lpr mice. J Immunol 145:1794–1798

    PubMed  CAS  Google Scholar 

  • Nandakumar KS, Holmdahl R (2008) Therapeutic cleavage of IgG: new avenues for treating inflammation. Trends Immunol 29:173–178

    PubMed  CAS  Google Scholar 

  • Nandakumar KS, Collin M, Olsen A, Nimmerjahn F, Blom AM, Ravetch JV, Holmdahl R (2007a) Endoglycosidase treatment abrogates IgG arthritogenicity: Importance of IgG glycosylation in arthritis. Eur J Immunol 37:2973–2982

    PubMed  CAS  Google Scholar 

  • Nandakumar KS, Johansson BP, Bjorck L, Holmdahl R (2007b) Blocking of experimental arthritis by cleavage of IgG antibodies in vivo. Arthritis Rheum 56:3253–3260

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2006) Fcgamma receptors: old friends and new family members. Immunity 24:19–28

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2007a) Antibodies, Fc receptors and cancer. Curr Opin Immunol 19:239–245

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2007b) The antiinflammatory activity of IgG: the intravenous IgG paradox. J Exp Med 204:11–15

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2008a) Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26:513–533

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Ravetch JV (2008b) Fc gamma receptors as regulators of immune responses. Nat Rev Immunol 8:34–47

    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

    PubMed  CAS  Google Scholar 

  • Nimmerjahn F, Anthony RM, Ravetch JV (2007) Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci USA 104:8433–8437

    PubMed  CAS  Google Scholar 

  • Otten MA, van der Bij GJ, Verbeek SJ, Nimmerjahn F, Ravetch JV, Beelen RH, van de Winkel JG, van Egmond M (2008) Experimental antibody therapy of liver metastases reveals functional redundancy between Fc gammaRI and Fc gammaRIV. J Immunol 181:6829–6836

    PubMed  CAS  Google Scholar 

  • Padigel UM, Farrell JP (2005) Control of infection with Leishmania major in susceptible BALB/c mice lacking the common gamma-chain for FcR is associated with reduced production of IL-10 and TGF-beta by parasitized cells. J Immunol 174:6340–6345

    PubMed  CAS  Google Scholar 

  • Pathan N, Faust SN, Levin M (2003) Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child 88:601–607

    PubMed  CAS  Google Scholar 

  • Perez-Bercoff D, David A, Sudry H, Barre-Sinoussi F, Pancino G (2003) Fcgamma receptor-mediated suppression of human immunodeficiency virus type 1 replication in primary human macrophages. J Virol 77:4081–4094

    PubMed  CAS  Google Scholar 

  • Radaev S, Motyka S, Fridman WH, Sautes-Fridman C, Sun PD (2001) The structure of a human type III Fcgamma receptor in complex with Fc. J Biol Chem 276:16469–16477

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ravetch JV, Nimmerjahn F (2008) Fc receptors. In: Paul WE (ed) Fundamental immunology, 5th edn. Lippincott-Raven, Philadelphia, pp 684–705

    Google Scholar 

  • Rodriguez ME, van der Pol WL, Sanders LA, van de Winkel JG (1999) Crucial role of FcgammaRIIa (CD32) in assessment of functional anti-Streptococcus pneumoniae antibody activity in human sera. J Infect Dis 179:423–433

    PubMed  CAS  Google Scholar 

  • Rodriguez ME, Hellwig SM, Hozbor DF, Leusen J, van der Pol WL, van de Winkel JG (2001) Fc receptor-mediated immunity against Bordetella pertussis. J Immunol 167:6545–6551

    PubMed  CAS  Google Scholar 

  • Rodriguez W, Mold C, Kataranovski M, Hutt JA, Marnell LL, Verbeek JS, Du Clos TW (2007) C-reactive protein-mediated suppression of nephrotoxic nephritis: role of macrophages, complement, and Fcgamma receptors. J Immunol 178:530–538

    PubMed  CAS  Google Scholar 

  • Rook GA, Steele J, Brealey R, Whyte A, Isenberg D, Sumar N, Nelson JL, Bodman KB, Young A, Roitt IM et al (1991) Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy. J Autoimmun 4:779–794

    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

    PubMed  CAS  Google Scholar 

  • Scallon BJ, Tam SH, McCarthy SG, Cai AN, Raju TS (2007) Higher levels of sialylated Fc glycans in immunoglobulin G molecules can adversely impact functionality. Mol Immunol 44:1524–1534

    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 

  • Schmidt RE, Gessner JE (2005) Fc receptors and their interaction with complement in autoimmunity. Immunol Lett 100:56–67

    PubMed  CAS  Google Scholar 

  • 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 Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 276:6591–6604

    PubMed  CAS  Google Scholar 

  • 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 Fcgamma RIII and antibody-dependent cellular toxicity. J Biol Chem 277:26733–26740, Epub 2002 May 1

    PubMed  CAS  Google Scholar 

  • 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 278:3466–3473, Epub 2002 Nov 8

    PubMed  CAS  Google Scholar 

  • Smith I, Vedeler C, Halstensen A (2003) FcgammaRIIa and FcgammaRIIIb polymorphisms were not associated with meningococcal disease in Western Norway. Epidemiol Infect 130:193–199

    PubMed  CAS  Google Scholar 

  • Sondermann P, Huber R, Oosthuizen V, Jacob U (2000) The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature 406:267–273

    PubMed  CAS  Google Scholar 

  • Sprague ER, Reinhard H, Cheung EJ, Farley AH, Trujillo RD, Hengel H, Bjorkman PJ (2008) The human cytomegalovirus Fc receptor gp68 binds the Fc CH2-CH3 interface of immunoglobulin G. J Virol 82:3490–3499

    PubMed  CAS  Google Scholar 

  • Stout RD, Herzenberg LA (1975) The Fc receptor on thymus-derived lymphocytes. I. Detection of a subpopulation of murine T lymphocytes bearing the Fc receptor. J Exp Med 142:611–621

    PubMed  CAS  Google Scholar 

  • Syed SN, Konrad S, Wiege K, Nieswandt B, Nimmerjahn F, Schmidt RE, Gessner JE (2009) Both FcgammaRIV and FcgammaRIII are essential receptors mediating type II and type III autoimmune responses via FcRgamma-LAT-dependent generation of C5a. Eur J Immunol 39:3343–3356

    PubMed  CAS  Google Scholar 

  • Sylvestre D, Clynes R, Ma M, Warren H, Carroll MC, Ravetch JV (1996) Immunoglobulin G-mediated inflammatory responses develop normally in complement-deficient mice. J Exp Med 184:2385–2392

    PubMed  CAS  Google Scholar 

  • Tackenberg B, Jelcic I, Baerenwaldt A, Oertel WH, Sommer N, Nimmerjahn F, Lunemann JD (2009) Impaired inhibitory Fc gamma receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci USA 106:4788–4792

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

    PubMed  CAS  Google Scholar 

  • Takeda A, Tuazon CU, Ennis FA (1988) Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science 242:580–583

    PubMed  CAS  Google Scholar 

  • Thomas-Rudolph D, Du Clos TW, Snapper CM, Mold C (2007) C-reactive protein enhances immunity to Streptococcus pneumoniae by targeting uptake to Fc gamma R on dendritic cells. J Immunol 178:7283–7291

    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

    PubMed  CAS  Google Scholar 

  • van de Geijn FE, Wuhrer M, Selman MH, Willemsen SP, de Man YA, Deelder AM, Hazes JM, Dolhain RJ (2009) Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study. Arthritis Res Ther 11:R193

    PubMed  Google Scholar 

  • Verma A, Ngundi MM, Meade BD, De Pascalis R, Elkins KL, Burns DL (2009) Analysis of the Fc gamma receptor-dependent component of neutralization measured by anthrax toxin neutralization assays. Clin Vaccine Immunol 16:1405–1412

    PubMed  CAS  Google Scholar 

  • Walker BD, Burton DR (2008) Toward an AIDS vaccine. Science 320:760–764

    PubMed  CAS  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, Epub 2003 Sep 15

    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, Epub 2004 Oct 13

    PubMed  CAS  Google Scholar 

  • Willcocks LC, Smith KG, Clatworthy MR (2009) Low-affinity Fcgamma receptors, autoimmunity and infection. Expert Rev Mol Med 11:e24

    PubMed  Google Scholar 

  • Wood P (2009) Primary antibody deficiency syndromes. Ann Clin Biochem 46:99–108

    PubMed  CAS  Google Scholar 

  • Woof JM, Burton DR (2004) Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol 4:89–99

    PubMed  CAS  Google Scholar 

  • Yee AM, Phan HM, Zuniga R, Salmon JE, Musher DM (2000) Association between FcgammaRIIa-R131 allotype and bacteremic pneumococcal pneumonia. Clin Infect Dis 30:25–28

    PubMed  CAS  Google Scholar 

  • Yoneto T, Waki S, Takai T, Tagawa Y, Iwakura Y, Mizuguchi J, Nariuchi H, Yoshimoto T (2001) A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection. J Immunol 166:6236–6241

    PubMed  CAS  Google Scholar 

  • Yuan FF, Wong M, Pererva N, Keating J, Davis AR, Bryant JA, Sullivan JS (2003) FcgammaRIIA polymorphisms in Streptococcus pneumoniae infection. Immunol Cell Biol 81:192–195

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We apologize to all our colleagues whose important work could not be cited directly due to limited amount of space. These references can be found in the different review articles cited in the manuscript. This work was supported by grants from the NIH (to J.V.R), by the German Research Foundation (FOR 832, SFB 643 to F.N.) and the Bavarian Genome Research Network (to F.N.).

Author information

Authors and Affiliations

  1. Chair of Genetics, University of Erlangen-Nuremberg, Staudtstr. 5, 91054, Erlangen, Germany

    Falk Nimmerjahn

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

    Jeffrey V. Ravetch

Authors
  1. Falk Nimmerjahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey V. Ravetch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Falk Nimmerjahn .

Editor information

Editors and Affiliations

  1. Emory Vaccine Center &, Yerkes National Primate Research Center, Emory University, Gatewood Rd. 954, Atlanta, 30329, Georgia, USA

    Rafi Ahmed

  2. Fac. Medicine, Dept. Medical Chemistry and Molecular, Kyoto University, Yoshida Konoe-cho, Kyoto, 606-8501, Japan

    Tasuku Honjo

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Nimmerjahn, F., Ravetch, J.V. (2010). FcγRs in Health and Disease. In: Ahmed, R., Honjo, T. (eds) Negative Co-Receptors and Ligands. Current Topics in Microbiology and Immunology, vol 350. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2010_86

Download citation

Publish with us

Policies and ethics

Search

Navigation