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Original

Complement deficiencies in humans and animals: Links to autoimmunity

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Pages 367-378 | Received 19 Jan 2006, Accepted 06 Apr 2006, Published online: 07 Jul 2009

References

  • Lachmann PJ, Muller-Eberhard HJ, Kunkel HG, Paronetto F. The localization of in vivo bound complement in tissue section. J Exp Med 1962; 115: 63–82
  • Elliott JA, Mathieson DR. Complement in disseminated (systemic) lupus erythematosus. AMA Arch Derm Syphilol 1953; 68: 119–128
  • Wedgwood RJP, Janeway CA. Serum complement in children with collagen diseases. Pediatrics 1953; 11: 569–581
  • Schur PH, Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med 1968; 278: 533–538
  • Agnello V. Association of systemic lupus erythematosus and SLE-like syndromes with hereditary and acquired complement deficiency states. Arthritis Rheum 1978; 21: S146–S152
  • Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol 2000; 76: 227–324
  • Dragon-Durey MA, Quartier P, Fremeaux-Bacchi V, et al. Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases. J Immunol 2001; 166: 7612–7616
  • Rupert KL, Moulds JM, Yang Y, et al. The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes. J Immunol 2002; 169: 1570–1578
  • Stone NM, Williams A, Wilkinson JD, Bird G. Systemic lupus erythematosus with C1q deficiency. Br J Dermatol 2000; 142: 521–524
  • Yang Y, Lhotta K, Chung EK, Eder P, Neumair F, Yu CY. Complete complement components C4A and C4B deficiencies in human kidney diseases and systemic lupus erythematosus. J Immunol 2004; 173: 2803–2814
  • Glass D, Raum D, Gibson D, Stillman JS, Schur PH. Inherited deficiency of the second component of complement. Rheumatic disease associations. J Clin Invest 1976; 58: 853–861
  • Klemperer MR, Woodworth HC, Rosen FS, Austen KF. Hereditary deficiency of the second component of complement (C′2) in man. J Clin Invest 1966; 45: 880–890
  • Imai K, Nakajima K, Eguchi K, et al. Homozygous C3 deficiency associated with IgA nephropathy. Nephron 1991; 59: 148–152
  • Nilsson UR, Nilsson B, Storm KE, Sjolin-Forsberg G, Hallgren R. Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis. Arthritis Rheum 1992; 35: 580–586
  • Sano Y, Nishimukai H, Kitamura H, et al. Hereditary deficiency of the third component of complement in two sisters with systemic lupus erythematosus-like symptoms. Arthritis Rheum 1981; 24: 1255–1260
  • Botto M, Walport MJ. Hereditary deficiency of C3 in animals and humans. Int Rev Immunol 1993; 10: 37–50
  • Hassig A, Borel JF, Amman P, Thon M, Butler R. Essentielle hypokomplentamie. Pathol Microbiol 1964; 27: 542–549
  • Inai S, Akagaki Y, Moriyama T, et al. Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors. Int Arch Allergy Appl Immunol 1989; 90: 274–279
  • Berkel AI, Birben E, Oner C, Oner R, Loos M, Petry F. Molecular, genetic and epidemiologic studies on selective complete C1q deficiency in Turkey. Immunobiology 2000; 201: 347–355
  • Deapen D, Escalante A, Weinrib L, et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 1992; 35: 311–318
  • Law SK, Dodds AW, Porter RR. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J 1984; 3: 1819–1823
  • Chung EK, Yang Y, Rennebohm RM, et al. Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21-TNX (RCCX) modules in the major histocompatibility complex. Am J Hum Gen 2002; 71: 823–837
  • Dangel AW, Mendoza AR, Baker BJ, et al. The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates. Immunogenetics 1994; 40: 425–436
  • Tassabehji M, Strachan T, Anderson M, Campbell RD, Collier S, Lako M. Identification of a novel family of human endogenous retroviruses and characterization of one family member, HERV-K(C4), located in the complement C4 gene cluster. Nucleic Acids Res 1994; 22: 5211–5217
  • Schneider PM, Witzel-Schlomp K, Rittner C, Zhang L. The endogenous retroviral insertion in the human complement C4 gene modulates the expression of homologous genes by antisense inhibition. Immunogenetics 2001; 53: 1–9
  • Yang Y, Chung EK, Zhou B, et al. Diversity in intrinsic strengths of the human complement system: Serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index. J Immunol 2003; 171: 2734–2745
  • Yang Y, Chung EK, Zhou B, et al. The intricate role of complement component C4 in human systemic lupus erythematosus. Curr Dir Autoimmun 2004; 7: 98–132
  • Lipscombe RJ, Sumiya M, Summerfield JA, Turner MW. Distinct physicochemical characteristics of human mannose binding protein expressed by individuals of differing genotype. Immunology 1995; 85: 660–667
  • Ip WK, Chan SY, Lau CS, Lau YL. Association of systemic lupus erythematosus with promoter polymorphisms of the mannose-binding lectin gene. Arthritis Rheum 1998; 41: 1663–1668
  • Lau YL, Lau CS, Chan SY, Karlberg J, Turner MW. Mannose-binding protein in Chinese patients with systemic lupus erythematosus. Arthritis Rheum 1996; 39: 706–708
  • Lee YH, Witte T, Momot T, et al. The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: Two case-control studies and a meta-analysis. Arthritis Rheum 2005; 52: 3966–3974
  • Sullivan KE, Wooten C, Goldman D, Petri M. Mannose-binding protein genetic polymorphisms in black patients with systemic lupus erythematosus. Arthritis Rheum 1996; 39: 2046–2051
  • Ohlenschlaeger T, Garred P, Madsen HO, Jacobsen S. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med 2004; 351: 260–267
  • Koide M, Shirahama S, Tokura Y, Takigawa M, Hayakawa M, Furukawa F. Lupus erythematosus associated with C1 inhibitor deficiency. J Dermatol 2002; 29: 503–507
  • Cacoub P, Fremeaux-Bacchi V, De Lacroix I, et al. A new type of acquired C1 inhibitor deficiency associated with systemic lupus erythematosus. Arthritis Rheum 2001; 44: 1836–1840
  • Nettis E, Colanardi MC, Loria MP, Vacca A. Acquired C1-inhibitor deficiency in a patient with systemic lupus erythematosus: A case report and review of the literature. Eur J Clin Invest 2005; 35: 781–784
  • Donaldson VH, Hess EV, McAdams AJ. Lupus-erythematosus-like disease in three unrelated women with hereditary angioneurotic edema. Ann Intern Med 1977; 86: 312–313
  • Ohi H, Yasugi T. Occurrence of C3 nephritic factor and C4 nephritic factor in membranoproliferative glomerulonephritis (MPGN). Clin Exp Immunol 1994; 95: 316–321
  • Walport MJ, Davies KA, Botto M, et al. C3 nephritic factor and SLE: Report of four cases and review of the literature. Q J Med 1994; 87: 609–615
  • Wisnieski JJ, Naff GB. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome. Arthritis Rheum 1989; 32: 1119–1127
  • Wisnieski JJ. Urticarial vasculitis. Curr Opin Rheumatol 2000; 12: 24–31
  • Nydegger UE, Lambert PH, Gerber H, Miescher PA. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q. J Clin Invest 1974; 54: 297–309
  • Hay FC, Nineham LJ, Roitt IM. Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase C1q. Clin Exp Immunol 1976; 24: 396–400
  • Tung KS, DeHoratius RJ, Williams RC. Study of circulating immune complex size in systemic lupus erythematosus. Clin Exp Immunol 1981; 43: 615–625
  • Kohro-Kawata J, Wener MH, Mannik M. The effect of high salt concentration on detection of serum immune complexes and autoantibodies to C1q in patients with systemic lupus erythematosus. J Rheumatol 2002; 29: 84–89
  • Siegert C, Daha M, Westedt ML, van der Voort E, Breedveld F. IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus. J Rheumatol 1991; 18: 230–234
  • Trendelenburg M, Marfurt J, Gerber I, Tyndall A, Schifferli JA. Lack of occurrence of severe lupus nephritis among anti-C1q autoantibody-negative patients. Arthritis Rheum 1999; 42: 187–188
  • Gunnarsson I, Ronnelid J, Huang YH, et al. Association between ongoing anti-C1q antibody production in peripheral blood and proliferative nephritis in patients with active systemic lupus erythematosus. Br J Rheumatol 1997; 36: 32–37
  • Mannik M, Wener MH. Deposition of antibodies to the collagen-like region of C1q in renal glomeruli of patients with proliferative lupus glomerulonephritis. Arthritis Rheum 1997; 40: 1504–1511
  • Hogarth MB, Norsworthy PJ, Allen PJ, et al. Autoantibodies to the collagenous region of C1q occur in three strains of lupus-prone mice. Clin Exp Immunol 1996; 104: 241–246
  • Trinder PK, Maeurer MJ, Schorlemmer HU, Loos M. Autoreactivity to mouse C1q in a murine model of SLE. Rheumatol Int 1995; 15: 117–120
  • Trouw LA, Groeneveld TW, Seelen MA, et al. Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J Clin Invest 2004; 114: 679–688
  • Botto M, Dell'Agnola C, Bygrave AE, et al. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 1998; 19: 56–59
  • Paul E, Pozdnyakova OO, Mitchell E, Carroll MC. Anti-DNA autoreactivity in C4-deficient mice. Eur J Immunol 2002; 32: 2672–2679
  • Chen Z, Koralov SB, Kelsoe G. Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2. J Exp Med 2000; 192: 1339–1352
  • Sekine H, Reilly CM, Molano ID, et al. Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice. J Immunol 2001; 166: 6444–6451
  • Stuart LM, Takahashi K, Shi L, Savill J, Ezekowitz RA. Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype. J Immunol 2005; 174: 3220–3226
  • Manderson AP, Botto M, Walport MJ. The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol 2004; 22: 431–456
  • Mitchell DA, Pickering MC, Warren J, et al. C1q deficiency and autoimmunity: The effects of genetic background on disease expression. J Immunol 2002; 168: 2538–2543
  • Bygrave AE, Rose KL, Cortes-Hernandez J, et al. Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice. PLoS Biol 2004; 2: E243
  • Wu X, Jiang N, Deppong C, et al. A role for the Cr2 gene in modifying autoantibody production in systemic lupus erythematosus. J Immunol 2002; 169: 1587–1592
  • Wang Y, Hu Q, Madri JA, Rollins SA, Chodera A, Matis LA. Amelioration of lupus-like autoimmune disease in NZB/WF1 mice after treatment with a blocking monoclonal antibody specific for complement component C5. Proc Natl Acad Sci USA 1996; 93: 8563–8568
  • Ravirajan CT, Wang Y, Matis LA, et al. Effect of neutralizing antibodies to IL-10 and C5 on the renal damage caused by a pathogenic human anti-dsDNA antibody. Rheumatology 2004; 43: 442–447
  • Schifferli JA, Ng YC, Peters DK. The role of complement and its receptor in the elimination of immune complexes. N Engl J Med 1986; 315: 488–495
  • Moldenhauer F, David J, Fielder AH, Lachmann PJ, Walport MJ. Inherited deficiency of erythrocyte complement receptor type 1 does not cause susceptibility to systemic lupus erythematosus. Arthritis Rheum 1987; 30: 961–966
  • Ross GD, Yount WJ, Walport MJ, et al. Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation. J Immunol 1985; 135: 2005–2014
  • Walport MJ, Lachmann PJ. Erythrocyte complement receptor type 1, immune complexes, and the rheumatic diseases. Arthritis Rheum 1988; 31: 153–158
  • Davies KA, Schifferli JA, Walport MJ. Complement deficiency and immune complex disease. Springer Semin Immunopathol 1994; 15: 397–416
  • Walport MJ. Lupus, DNase and defective disposal of cellular debris. Nat Genet 2000; 25: 135–136
  • Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 1994; 179: 1317–1330
  • Rosen A, Casciola-Rosen L, Ahearn J. Novel packages of viral and self-antigens are generated during apoptosis. J Exp Med 1995; 181: 1557–1561
  • Cullis PR, de Kruijff B. Lipid polymorphism and the functional roles of lipids in biological membranes. Biochim Biophys Acta 1979; 559: 399–420
  • Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol 1992; 148: 2207–2216
  • Casciola-Rosen L, Rosen A, Petri M, Schlissel M. Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: Implications for coagulation events and antigenic spread in systemic lupus erythematosus. Proc Natl Acad Sci USA 1996; 93: 1624–1629
  • Mevorach D, Zhou JL, Song X, Elkon KB. Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 1998; 188: 387–392
  • Chang MK, Binder CJ, Miller YI, et al. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med 2004; 200: 1359–1370
  • Bondanza A, Zimmermann VS, Dell'Antonio G, et al. Requirement of dying cells and environmental adjuvants for the induction of autoimmunity. Arthritis Rheum 2004; 50: 1549–1560
  • Georgiev M, Agle LM, Chu JL, Elkon KB, Ashany D. Mature dendritic cells readily break tolerance in normal mice but do not lead to disease expression. Arthritis Rheum 2005; 52: 225–238
  • Korb LC, Ahearn JM. C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: Complement deficiency and systemic lupus erythematosus revisited. J Immunol 1997; 158: 4525–4528
  • Mevorach D, Mascarenhas JO, Gershov D, Elkon KB. Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 1998; 188: 2313–2320
  • Quartier P, Potter PK, Ehrenstein MR, Walport MJ, Botto M. Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur J Immunol 2005; 35: 252–260
  • Taylor PR, Carugati A, Fadok VA, et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 2000; 192: 359–366
  • Navratil JS, Watkins SC, Wisnieski JJ, Ahearn JM. The globular heads of C1q specifically recognize surface blebs of apoptotic vascular endothelial cells. J Immunol 2001; 166: 3231–3239
  • Nauta AJ, Trouw LA, Daha MR, et al. Direct binding of C1q to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 2002; 32: 1726–1736
  • Ogden CA, deCathelineau A, Hoffmann PR, et al. C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 2001; 194: 781–795
  • Vandivier RW, Ogden CA, Fadok VA, et al. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: Calreticulin and CD91 as a common collectin receptor complex. J Immunol 2002; 169: 3978–3986
  • Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41: 1241–1250
  • Grootscholten C, van Bruggen MC, van der Pijl JW, et al. Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis. Arthritis Rheum 2003; 48: 1355–1362
  • van Bruggen MC, Kramers C, Walgreen B, et al. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis. Nephrol Dial Transplant 1997; 12: 57–66
  • Amoura Z, Piette JC, Chabre H, et al. Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: Correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum 1997; 40: 2217–2225
  • Baumann I, Kolowos W, Voll RE, et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 2002; 46: 191–201
  • Gershov D, Kim S, Brot N, Elkon KB. C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: Implications for systemic autoimmunity. J Exp Med 2000; 192: 1353–1364
  • Kim SJ, Gershov D, Ma X, Brot N, Elkon KB. I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation. J Exp Med 2002; 196: 655–665
  • Ogden CA, Kowalewski R, Peng Y, Montenegro V, Elkon KB. IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity 2005; 38: 259–264
  • Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci USA 2000; 97: 1184–1189
  • Ehrenstein MR, Cook HT, Neuberger MS. Deficiency in serum immunoglobulin (Ig)M predisposes to development of IgG autoantibodies. J Exp Med 2000; 191: 1253–1258
  • Gaipl US, Beyer TD, Heyder P, et al. Cooperation between C1q and DNase I in the clearance of necrotic cell-derived chromatin. Arthritis Rheum 2004; 50: 640–649
  • Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Moroy T. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Gen 2000; 25: 177–181
  • Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 1998; 101: 890–898
  • Huynh ML, Fadok VA, Henson PM. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest 2002; 109: 41–50
  • Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature 1997; 390: 350–351
  • Gao Y, Herndon JM, Zhang H, Griffith TS, Ferguson TA. Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis. J Exp Med 1998; 188: 887–896
  • Chen W, Frank ME, Jin W, Wahl SM. TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 2001; 14: 715–725
  • Albert ML, Pearce SF, Francisco LM, et al. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 1998; 188: 1359–1368
  • Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392: 86–89
  • Ronchetti A, Rovere P, Iezzi G, et al. Immunogenicity of apoptotic cells in vivo: Role of antigen load, antigen-presenting cells, and cytokines. J Immunol 1999; 163: 130–136
  • Rovere P, Vallinoto C, Bondanza A, et al. Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol 1998; 161: 4467–4471
  • Savill J, Dransfield I, Gregory C, Haslett C. A blast from the past: Clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2002; 2: 965–975
  • Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 2000; 191: 423–434
  • Banchereau J, Pascual V, Palucka AK. Autoimmunity through cytokine-induced dendritic cell activation. Immunity 2004; 20: 539–550
  • Crow MK. Interferon-alpha: A new target for therapy in systemic lupus erythematosus?. Arthritis Rheum 2003; 48: 2396–2401
  • Lovgren T, Eloranta ML, Bave U, Alm GV, Ronnblom L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum 2004; 50: 1861–1872
  • Carroll MC. A protective role for innate immunity in systemic lupus erythematosus. Nat Rev Immunol 2004; 4: 825–831
  • Ellman L, Green I, Judge F, Frank MM. In vivo studies in C4-deficient guinea pigs. J Exp Med 1971; 134: 162–175
  • Carroll MC. The role of complement and complement receptors in induction and regulation of immunity. Ann Rev Immunol 1998; 1998: 545–568
  • Pepys MB. Role of complement in induction of antibody production in vivo. Effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J Exp Med 1974; 140: 126–145
  • Dempsey PW, Allison ME, Akkaraju S, Goodnow CC, Fearon DT. C3d of complement as a molecular adjuvant: Bridging innate and acquired immunity. Science 1996; 271: 348–350
  • Prodeus AP, Goerg S, Shen LM, et al. A critical role for complement in maintenance of self-tolerance. Immunity 1998; 9: 721–731
  • Cutler AJ, Cornall RJ, Ferry H, Manderson AP, Botto M, Walport MJ. Intact B cell tolerance in the absence of the first component of the classical complement pathway. Eur J Immunol 2001; 31: 2087–2093

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