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Specific IgM and Regulation of Antibody Responses

  • Anna Sörman
  • Birgitta Heyman
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 408)

Abstract

Specific IgM, administered together with the antigen it recognizes, enhances primary antibody responses, formation of germinal centers, and priming for secondary antibody responses. The response to all epitopes on the antigen to which IgM binds is usually enhanced. IgM preferentially enhances responses to large antigens such as erythrocytes, malaria parasites, and keyhole limpet hemocyanine. In order for an effect to be seen, antigens must be administered in suboptimal concentrations and in close temporal relationship to the IgM. Enhancement is dependent on the ability of IgM to activate complement, but the lytic pathway is not required. Enhancement does not take place in mice lacking complement receptors 1 and 2 (CR1/2) suggesting that the role of IgM is to generate C3 split products, i.e., the ligands for CR1/2. In mice, these receptors are expressed on follicular dendritic cells (FDCs) and B cells. Optimal IgM-mediated enhancement requires that both cell types express CR1/2, but intermediate enhancement is seen when only FDCs express the receptors and low enhancement when only B cells express them. These observations imply that IgM-mediated enhancement works through several, non-mutually exclusive, pathways. Marginal zone B cells can transport IgM-antigen-complement complexes, bound to CR1/2, from the marginal zone and deposit them onto FDCs. In addition, co-crosslinking of the BCR and the CR2/CD19/CD81 co-receptor complex may enhance signaling to specific B cells, a mechanism likely to be involved in induction of early extrafollicular antibody responses.

References

  1. Adachi T, Harumiya S, Takematsu H, Kozutsumi Y, Wabl M, Fujimoto M, Tedder TF (2012) CD22 serves as a receptor for soluble IgM. Eur J Immunol 42(1):241–247CrossRefPubMedGoogle Scholar
  2. Ahearn JM, Fischer MB, Croix D, Goerg S, Ma M, Xia J, Zhou X, Howard RG, Rothstein TL, Carroll MC (1996) Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity 4:251–262CrossRefPubMedGoogle Scholar
  3. Applequist SE, Dahlström J, Jiang N, Molina H, Heyman B (2000) Antibody production in mice deficient for complement receptors 1 and 2 can be induced by IgG/Ag and IgE/Ag, but not IgM/Ag complexes. J Immunol 165:2398–2403CrossRefPubMedGoogle Scholar
  4. Arnon TI, Horton RM, Grigorova IL, Cyster JG (2013) Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress. Nature 493(7434):684–688CrossRefPubMedGoogle Scholar
  5. Bergström JJ, Heyman B (2015) IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors. PLoS ONE 10(11):e0143841CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bernardo L, Yu H, Amash A, Zimring JC, Lazarus AH (2015) IgG-mediated immune suppression to erythrocytes by polyclonal antibodies can occur in the absence of activating or inhibitory Fc-gamma receptors in a full mouse model. J Immunol 195(5):2224–2230CrossRefPubMedGoogle Scholar
  7. Boackle SA, Holers VM, Karp DR (1997) CD21 augments antigen presentation in immune individuals. Eur J Immunol 27(1):122–129CrossRefPubMedGoogle Scholar
  8. Borsos T, Rapp HJ (1965) Hemolysin titration based on fixation of the activated first component of complement: evidence that one molecule of hemolysin suffices to sensitize an erythrocyte. J Immunol 95:559–566PubMedGoogle Scholar
  9. Bowman JM (1988) The prevention of Rh immunization. Transfus Med Rev 2:129–150CrossRefPubMedGoogle Scholar
  10. Carlsson F, Getahun A, Rutemark C, Heyman B (2009) Impaired antibody responses but normal proliferation of specific CD4+ T cells in mice lacking complement receptors 1 and 2. Scand J Immunol 70(2):77–84CrossRefPubMedGoogle Scholar
  11. Carroll MC (2008) Complement and humoral immunity. Vaccine 26(Suppl 8):28–33CrossRefGoogle Scholar
  12. Carter RH, Spycher MO, Ng YC, Hoffmann R, Fearon DT (1988) Synergistic interaction between complement receptor type 2 and membrane IgM on B-lymphocytes. J Immunol 141:457–463PubMedGoogle Scholar
  13. Chan TD, Brink R (2012) Affinity-based selection and the germinal center response. Immunol Rev 247(1):11–23CrossRefPubMedGoogle Scholar
  14. Cinamon G, Zachariah MA, Lam OM, Foss FW Jr, Cyster JG (2008) Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol 9(1):54–62CrossRefPubMedGoogle Scholar
  15. Clarke CA, Donohoe WTA, Woodrow JC, Finn R, Krevans JR, Kulke W, Lehane D, Sheppard PM (1963) Further experimental studies on the prevention of Rh haemolytic disease. Br Med Journal 1:979–984CrossRefGoogle Scholar
  16. Corley RB, Morehouse EM, Ferguson AR (2005) IgM accelerates affinity maturation. Scand J Immunol 62(Suppl 1):55–61CrossRefPubMedGoogle Scholar
  17. Coulie P, Van Snick J (1985) Enhancement of IgG anti-carrier responses by IgG2-anti-hapten antibodies in mice. Eur J Immunol 15:793–798CrossRefPubMedGoogle Scholar
  18. Coutinho A, Forni L (1981) The enhancement of antibody response by IgM antibodies is dependent on antigen-specific T helper cells. Immunobiology 158:182–190CrossRefPubMedGoogle Scholar
  19. Cutler AJ, Botto M, van Essen D, Rivi R, Davies KA, Gray D, Walport MJ (1998) T cell-dependent immune response in C1q-deficient mice: defective interferon g production by antigen-specific T cells. J Exp Med 187:1789–1797CrossRefPubMedPubMedCentralGoogle Scholar
  20. Czajkowsky DM, Shao Z (2009) The human IgM pentamer is a mushroom-shaped molecule with a flexural bias. Proc Natl Acad Sci U S A 106(35):14960–14965CrossRefPubMedPubMedCentralGoogle Scholar
  21. Da Costa XJ, Brockman MA, Alicot E, Ma M, Fischer MB, Zhou X, Knipe DM, Carroll MC (1999) Humoral response to herpes simplex virus is complement-dependent. Proc Natl Acad Sci U S A 96(22):12708–12712CrossRefPubMedPubMedCentralGoogle Scholar
  22. Davis AC, Roux KH, Shulman MJ (1988) On the structure of polymeric IgM. Eur J Immunol 18(7):1001–1008CrossRefPubMedGoogle Scholar
  23. de Jong JM, Schuurhuis DH, Ioan-Facsinay A, Welling MM, Camps MG, van der Voort EI, Huizinga TW, Ossendorp F, Verbeek JS, Toes RE (2006) Dendritic cells, but not macrophages or B cells, activate major histocompatibility complex class II-restricted CD4+ T cells upon immune-complex uptake in vivo. Immunology 119(4):499–506CrossRefPubMedPubMedCentralGoogle Scholar
  24. Dempsey PW, Allison MED, Akkaraju S, Goodnow CC, Fearon DT (1996) C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271:348–350CrossRefPubMedGoogle Scholar
  25. Dennert G (1971) The mechanism of antibody-induced stimulation and inhibition of the immune response. J Immunol 106:951–955PubMedGoogle Scholar
  26. Dennert G, Pohlit H, Rajewsky K (1971) Co-operative antibody: a concentrating device. In: Mäkelä O, Cross A, Kosunen TU (eds) Cell interactions and receptor antibodies in immune responses. Academic Press Limited, London, pp 3–7Google Scholar
  27. Diaz de Ståhl T, Dahlström J, Carroll MC, Heyman B (2003) A role for complement in feedback-enhancement of antibody responses by IgG3. J Exp Med 197:1183–1190CrossRefPubMedGoogle Scholar
  28. Ding ZJ, Bergman A, Rutemark C, Ouchida R, Ohno H, Wang JY, Heyman B (2013) Complement-activating IgM enhances the humoral but not the T cell immune response in mice. PLoS ONE 8(11):e81299–e81299CrossRefPubMedPubMedCentralGoogle Scholar
  29. Donius LR, Handy JM, Weis JJ, Weis JH (2013) Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1. J Immunol 191(1):434–447CrossRefPubMedPubMedCentralGoogle Scholar
  30. Ehrenstein MR, O’Keefe TL, Davies SL, Neuberger MS (1998) Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response. Proc Natl Acad Sci U S A 95(17):10089–10093CrossRefPubMedPubMedCentralGoogle Scholar
  31. Enriquez-Rincon F, Klaus GGB (1984) Differing effects of monoclonal anti-hapten antibodies on humoral responses to soluble or particulate antigens. Immunology 52:129–136PubMedPubMedCentralGoogle Scholar
  32. Feinstein A, Munn EA (1969) Conformation of the free and antigen-bound IgM antibody molecules. Nature 224(5226):1307–1309CrossRefPubMedGoogle Scholar
  33. Ferguson AR, Youd ME, Corley RB (2004) Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells. Int Immunol 16(10):1411–1422CrossRefPubMedGoogle Scholar
  34. Forni L, Coutinho A, Köhler G, Jerne N (1980) IgM antibodies induce the production of antibodies of the same specificity. Proc Natl Acad Sci USA 77:1125–1128CrossRefPubMedPubMedCentralGoogle Scholar
  35. Getahun A, Dahlström J, Wernersson S, Heyman B (2004) IgG2a-mediated enhancement of Ab- and T-cell responses and its relation to inhibitory and activating FcgRs. J Immunol 172:5269–5276CrossRefPubMedGoogle Scholar
  36. Getahun A, Hjelm F, Heyman B (2005) IgE enhances antibody and T cell responses in vivo via CD23+ B Cells. J Immunol 175(3):1473–1482CrossRefPubMedGoogle Scholar
  37. Gitlin AD, Shulman Z, Nussenzweig MC (2014) Clonal selection in the germinal centre by regulated proliferation and hypermutation. Nature 509(7502):637–640CrossRefPubMedPubMedCentralGoogle Scholar
  38. Gustavsson S, Kinoshita T, Heyman B (1995) Antibodies to murine complement receptor 1 and 2 can inhibit the antibody response in vivo without inhibiting T-helper cell induction. J Immunol 154:6524–6528PubMedGoogle Scholar
  39. Hamano Y, Arase H, Saisho H, Saito T (2000) Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses. J Immunol 164(12):6113–6119CrossRefPubMedGoogle Scholar
  40. Harte PG, Cooke A, Playfair JHL (1983) Specific monoclonal IgM is a potent adjuvant in murine malaria vaccination. Nature 302:256–258CrossRefPubMedGoogle Scholar
  41. Heesters BA, Chatterjee P, Kim YA, Gonzalez SF, Kuligowski MP, Kirchhausen T, Carroll MC (2013) Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity 38(6):1164–1175CrossRefPubMedPubMedCentralGoogle Scholar
  42. Heesters BA, Myers RC, Carroll MC (2014) Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol 14(7):495–504CrossRefPubMedGoogle Scholar
  43. Henningsson F, Ding Z, Dahlin JS, Linkevicius M, Carlsson F, Grönvik KO, Hallgren J, Heyman B (2011) IgE-mediated enhancement of CD4+ T cell responses in mice requires antigen presentation by CD11c + cells and not by B cells. PLoS ONE 6(7):e21760CrossRefPubMedPubMedCentralGoogle Scholar
  44. Henry C, Jerne N (1968) Competition of 19S and 7S antigen receptors in the regulation of the primary immune response. J Exp Med 128:133–152CrossRefPubMedPubMedCentralGoogle Scholar
  45. Heyman B (2000) Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu Rev Immunol 18:709–737CrossRefPubMedGoogle Scholar
  46. Heyman B, Andrighetto S, Wigzell H (1982) Antigen dependent IgM-mediated enhancement of the sheep erythrocyte response in mice. Evidence for induction of B cells with specificities other than that of the injected antibodies. J Exp Med 155:994–1009CrossRefPubMedPubMedCentralGoogle Scholar
  47. Heyman B, Hobbs M, Weigle WO (1985) IgM-mediated enhancement of in vivo anti-sheep erythrocyte antibody responses: Isotype analysis of the enhanced responses. Cell Immunol 92:134–141CrossRefPubMedGoogle Scholar
  48. Heyman B, Pilström L, Shulman MJ (1988a) Complement activation is required for IgM-mediated enhancement of the antibody response. J Exp Med 167:1999–2004CrossRefPubMedGoogle Scholar
  49. Heyman B, Wiersma E, Nose M (1988b) Complement activation is not required for IgG-mediated suppression of the antibody response. Eur J Immunol 18:1739–1743CrossRefPubMedGoogle Scholar
  50. Heyman B, Wiersma EJ, Kinoshita T (1990) In vivo inhibition of the antibody response by a monoclonal complement receptor specific antibody. J Exp Med 172:665–668CrossRefPubMedGoogle Scholar
  51. Heyman B, Wigzell H (1985) IgM enhances and IgG suppresses immunological memory in mice. Scand J Immunol 21:255–266CrossRefPubMedGoogle Scholar
  52. Hjelm F, Carlsson F, Getahun A, Heyman B (2006) Antibody-mediated regulation of the immune response. Scand J Immunol 64(3):177–184CrossRefPubMedGoogle Scholar
  53. Hjelm F, Karlsson MCI, Heyman B (2008) A novel B-cell mediated transport of IgE-immune complexes to the follicle of the spleen. J Immunol 180:6604–6610CrossRefPubMedGoogle Scholar
  54. Honjo K, Kubagawa Y, Jones DM, Dizon B, Zhu Z, Ohno H, Izui S, Kearney JF, Kubagawa H (2012) Altered Ig levels and antibody responses in mice deficient for the Fc receptor for IgM (FcmuR). Proc Natl Acad Sci U S A 109(39):15882–15887CrossRefPubMedPubMedCentralGoogle Scholar
  55. Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125C(1–2):373–389Google Scholar
  56. Jerne NK, Nordin AA (1963) Plaque formation in agar by single antibody-producing cells. Science 140:405CrossRefGoogle Scholar
  57. Johansen FE, Braathen R, Brandtzaeg P (2000) Role of J chain in secretory immunoglobulin formation. Scand J Immunol 52(3):240–248CrossRefPubMedGoogle Scholar
  58. Karlsson MCI, Getahun A, Heyman B (2001) FcgRIIB in IgG-mediated suppression of antibody responses: different impact in vivo and in vitro. J Immunol 167:5558–5564CrossRefPubMedGoogle Scholar
  59. Karlsson MCI, Wernersson S, Diaz de Ståhl T, Gustavsson S, Heyman B (1999) Efficient IgG-mediated suppression of primary antibody responses in Fc-gamma receptor-deficient mice. Proc Natl Acad Sci USA 96:2244–2249CrossRefPubMedPubMedCentralGoogle Scholar
  60. Kinoshita T, Takeda J, Hong K, Kozono H, Sakai H, Inoue K (1988) Monoclonal antibodies to mouse complement receptor type 1 (CR1). Their use in a distribution study showing that mouse erythrocytes and pltelets are CR1-negative. J Immunol 140:3066PubMedGoogle Scholar
  61. Lehner P, Hutchings P, Lydyard PM, Cooke A (1983) Regulation of the immune response by antibody II. IgM-mediated enhancement: dependency on antigen dose, T-cell requirement and lack of evidence for an idiotype-related mechanism. Immunology 50:503–509PubMedPubMedCentralGoogle Scholar
  62. Link A, Zabel F, Schnetzler Y, Titz A, Brombacher F, Bachmann MF (2012) Innate immunity mediates follicular transport of particulate but not soluble protein antigen. J Immunol 188(8):3724–3733CrossRefPubMedGoogle Scholar
  63. MacLennan IC, Toellner KM, Cunningham AF, Serre K, Sze DM, Zuniga E, Cook MC, Vinuesa CG (2003) Extrafollicular antibody responses. Immunol Rev 194:8–18CrossRefPubMedGoogle Scholar
  64. Matsumoto AK, Martin DR, Carter RH, Klickstein LB, Ahearn JM, Fearon DT (1993) Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. J Exp Med 178(4):1407–1417CrossRefPubMedGoogle Scholar
  65. Molina H, Holers VM, Li B, Fang Y-F, Mariathasan S, Goellner J, Strauss-Schoenberger J, Karr RW, Chaplin DD (1996) Markedly impaired humoral immune responses in mice deficient in complement receptors 1 and 2. Proc Natl Acad Sci USA 93:3357–3361CrossRefPubMedPubMedCentralGoogle Scholar
  66. Möller G, Wigzell H (1965) Antibody synthesis at the cellular level. Antibody-induced suppression of 19S and 7S antibody responses. J Exp Med 121:969–989CrossRefPubMedPubMedCentralGoogle Scholar
  67. Nolte MA, Belien JA, Schadee-Eestermans I, Jansen W, Unger WW, van Rooijen N, Kraal G, Mebius RE (2003) A conduit system distributes chemokines and small blood-borne molecules through the splenic white pulp. J Exp Med 198(3):505–512CrossRefPubMedPubMedCentralGoogle Scholar
  68. Ohno T, Kubagawa H, Sanders SK, Cooper MD (1990) Biochemical nature of an Fc mu receptor on human B-lineage cells. J Exp Med 172(4):1165–1175CrossRefPubMedGoogle Scholar
  69. Ouchida R, Mori H, Hase K, Takatsu H, Kurosaki T, Tokuhisa T, Ohno H, Wang JY (2012) Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. Proc Natl Acad Sci U S A 109(40):2699–2706CrossRefGoogle Scholar
  70. Pearlman DS (1967) The influence of antibodies on immunologic responses. The effect on the response to particulate antigen in the rabbit. J Exp Med 126:127–148CrossRefPubMedPubMedCentralGoogle Scholar
  71. Pepys MB (1974) 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 140:126–145CrossRefPubMedPubMedCentralGoogle Scholar
  72. Powell R, Hutchings P, Cooke A, Lydyard PM (1982) Antibody mediated regulation of immune responses: I. Enhancement of specific antibody responses through IgM antibodies. Immunol Lett 4(5):253–258CrossRefPubMedGoogle Scholar
  73. Rutemark C, Alicot E, Bergman A, Ma M, Getahun A, Ellmerich S, Carroll MC, Heyman B (2011) Requirement for complement in antibody responses is not explained by the classic pathway activator IgM. Proc Natl Acad Sci U S A 108(43):934–942CrossRefGoogle Scholar
  74. Rutemark C, Bergman A, Getahun A, Hallgren J, Henningsson F, Heyman B (2012) Complement receptors 1 and 2 in murine antibody responses to IgM-complexed and uncomplexed sheep erythrocytes. PLoS ONE 7(7):e41968CrossRefPubMedPubMedCentralGoogle Scholar
  75. Schrader JW (1973) Regulation of the immune response by IgM antibody: a paradoxical suppression of the in vitro primary immune response to sheep erythrocytes by IgM. Aust J Exp Biol Med Sci 51:333–346CrossRefPubMedGoogle Scholar
  76. Schwickert TA, Victora GD, Fooksman DR, Kamphorst AO, Mugnier MR, Gitlin AD, Dustin ML, Nussenzweig MC (2011) A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center. J Exp Med 208(6):1243–1252CrossRefPubMedPubMedCentralGoogle Scholar
  77. Shibuya A, Sakamoto N, Shimizu Y, Shibuya K, Osawa M, Hiroyama T, Miyabayashi T, Sakano S, Tsuji T, Nakayama E, Ohillips JH, Lanier LL (2000) Fcα/μ receptor mediates endocytosis of IgM-coated microbes. Nat Immunol 1(5):441–446CrossRefPubMedGoogle Scholar
  78. Shulman MJ, Collins C, Pennell N, Hozumi N (1987) Complement activation by IgM: evidence for the importance of the third constant domain of the µ heavy chain. Eur J Immunol 17:549–554CrossRefPubMedGoogle Scholar
  79. Shulman Z, Gitlin AD, Targ S, Jankovic M, Pasqual G, Nussenzweig MC, Victora GD (2013) T follicular helper cell dynamics in germinal centers. Science 341(6146):673–677CrossRefPubMedPubMedCentralGoogle Scholar
  80. Strannegård Ö, Belin L (1971) Enhancement of reagin formation in rabbits by passively administered 19S antibody. Immunology 20:427–431PubMedPubMedCentralGoogle Scholar
  81. Sörman A, Zhang L, Ding Z, Heyman B (2014) How antibodies use complement to regulate antibody responses. Mol Immunol 61(2):79–88CrossRefPubMedGoogle Scholar
  82. Thornton BP, Vetvicka V, Ross GD (1996) Function of C3 in a humoral response: iC3b/C3dg bound to an immune complex generated with natural antibody and a primary antigen promotes antigen uptake and the expression of co-stimulatory molecules by all B cells, but only stimulates immunoglobulin synthesis by antigen-specific B cells. Clin Exp Immunol 104(3):531–537CrossRefPubMedPubMedCentralGoogle Scholar
  83. Thyphronitis G, Kinoshita T, Inoue K, Schweinle JE, Tsokos GC, Metcalf ES, Finkelman FD, Balow JE (1991) Modulation of mouse complement receptors 1 and 2 suppresses antibody responses in vivo. J Immunol 147:224–230PubMedGoogle Scholar
  84. Uhr JW, Möller G (1968) Regulatory effect of antibody on the immune response. Adv Immunol 8:81–127CrossRefPubMedGoogle Scholar
  85. Victora GD, Schwickert TA, Fooksman DR, Kamphorst AO, Meyer-Hermann M, Dustin ML, Nussenzweig MC (2010) Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143(4):592–605CrossRefPubMedPubMedCentralGoogle Scholar
  86. Vinuesa CG, Linterman MA, Goodnow CC, Randall KL (2010) T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev 237(1):72–89CrossRefPubMedGoogle Scholar
  87. Wason WM (1973) Regulation of the immune response with antigen specific IgM antibody: a dual role. J Immunol 110:1245–1252PubMedGoogle Scholar
  88. Wernersson S, Karlsson M, Dahlström J, Mattsson R, Verbeek JS, Heyman B (1999) IgG-mediated enhancement of Ab responses is low in FcRg chain deficient mice and increased in FcgRII deficient mice. J Immunol 163:618–622PubMedGoogle Scholar
  89. Whited Collisson E, Andersson B, Lamon EW (1984) Avidities of hapten-specific antibodies when the responses are modulated by anti-carrier antibodies. Immunology 53:443–449PubMedPubMedCentralGoogle Scholar
  90. Whited Collisson E, Andersson B, Rönnholm M, Lamon E (1983) Potentiation of antibody responses by specific IgM: Specificity and thymus dependency. Cell Immunol 79:44–55CrossRefGoogle Scholar
  91. Wiersma EJ, Coulie PG, Heyman B (1989) Dual immunoregulatory effects of monoclonal IgG-antibodies: suppression and enhancement of the antibody response. Scand J Immunol 29:439–448CrossRefPubMedGoogle Scholar
  92. Wiersma EJ, Kinoshita T, Heyman B (1991) Inhibition of immunological memory and T-independent humoral responses by monoclonal antibodies specific for murine complement receptors. Eur J Immunol 21:2501–2506CrossRefPubMedGoogle Scholar
  93. Youd ME, Ferguson AR, Corley RB (2002) Synergistic roles of IgM and complement in antigen trapping and follicular localization. Eur J Immunol 32:2328–2337CrossRefPubMedGoogle Scholar
  94. Zhang L, Ding Z, Xu H, Heyman B (2014) Marginal zone B cells transport IgG3-immune complexes to splenic follicles. J Immunol 193(4):1681–1689CrossRefPubMedGoogle Scholar
  95. Zhang Y, Meyer-Hermann M, George LA, Figge MT, Khan M, Goodall M, Notley CA, Ehrenstein MR, Kosco-Vilbois M, Toellner KM (2013) Germinal center B cells govern their own fate via antibody feedback. Journal of Experimental Medicine 210(3):457–464CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Medical Biochemistry and MicrobiologyUppsala UniversityUppsalaSweden

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