Skip to main content
SpringerLink
Log in

Role of the CD19 and CD21/35 Receptor Complex in Innate Immunity, Host Defense and Autoimmunity

  • Conference paper
Mechanisms of Lymphocyte Activation and Immune Regulation X

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 560))

Abstract

Humoral immune responses to foreign and self-antigens must be tightly regulated to facilitate protective immunity to pathogens while avoiding autoimmune responses. The outcome of these responses is determined in part by signals generated through the B lymphocyte antigen receptor (BCR). These signals are further supplemented and fine- tuned by other cell-surface molecules that modify and provide a context for BCR signal transduction. Such molecules, or “response regulators”, influence these events by positively or negatively biasing the context of BCR signaling, thus establishing appropriate signaling thresholds. Response regulators amplify or dampen BCR signaling by regulating the activity of intracellular kinases, phosphatases, and other effector proteins. Included among the list of BCR signal transduction response regulators is CD19, which integrates multiple intracellular signaling pathways. On the B cell surface, CD19 interacts directly with CD21 (complement receptor 2, CR2), a receptor for the C3d complement cleavage product that forms covalent bonds with foreign Ags or immune complexes to effectively link innate and acquired immunity. This review summarizes recent findings that have clarified how the CD19/CD21 receptor complex functions to regulate B cell responses in host defense and autoimmunity.

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 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

8. References

  1. T. F. Tedder, Response-regulators of B lymphocyte signaling thresholds provide a context for antigen receptor signal transduction. Semin. Immunol. 10, 259–265 (1998).

    Article  PubMed  CAS  Google Scholar 

  2. S. Sato, D. A. Steeber, P. J. Jansen and T. F. Tedder, CD19 expression levels regulate B lymphocyte development: human CD19 restores normal function in mice lacking endogenous CD19. J. Immunol. 158, 4662–4669 (1997).

    PubMed  CAS  Google Scholar 

  3. S. Sato, N. Ono, D. A. Steeber, D. S. Pisetsky and T. F. Tedder, CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J. Immunol. 157, 4371–4378 (1996).

    PubMed  CAS  Google Scholar 

  4. T. F. Tedder and C. M. Isaacs, Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes: A new member of the immunoglobulin superfamily. J. Immunol. 143, 712–717 (1989).

    PubMed  CAS  Google Scholar 

  5. L.-J. Zhou, D. C. Ord, A. L. Hughes and T. F. Tedder, Structure and domain organization of the CD19 antigen of human, mouse and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain. J. Immunol. 147, 1424–1432 (1991).

    PubMed  CAS  Google Scholar 

  6. I. Krop, A. L. Shaffer, D. T. Fearon and M. S. Schlissel, The signaling activity of murine CD19 is regulated during B cell development. J. Immunol. 157, 48–56 (1996).

    PubMed  CAS  Google Scholar 

  7. A. W. Boyd, K. C. Anderson, A. S. Freedman, D. C. Fisher, B. Slaughenhoupt, S. F. Schlossman and L. M. Nadler, Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody. J. Immunol. 134, 1516–1523 (1985).

    PubMed  CAS  Google Scholar 

  8. L. E. Bradbury, G. S. Kansas, S. Levy, R. L. Evans and T. F. Tedder, The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. J. Immunol. 149, 2841–2850 (1992).

    PubMed  CAS  Google Scholar 

  9. S. Levy, S. C. Todd and H. T. Maecker, CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system Annu. Rev. Immunol 16, 89–110 (1998).

    Article  PubMed  CAS  Google Scholar 

  10. H. T. Maecker and S. Levy Normal lymphocyte development but delayed humoral immune response in CD81-null mice. J. Exp. Med. 185, 1505–1510 (1997).

    Article  PubMed  CAS  Google Scholar 

  11. T. Miyazaki, U. Muller and K. S. Campbell, Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81. EMBO J. 16, 4217–4225 (1997).

    Article  PubMed  CAS  Google Scholar 

  12. E. N. Tsitsikov, J.-C. Gutierrez-Ramos and R. S. Geha, Impaired CD19 expression and signaling, enhanced antibody response to type II T-independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc. Natl. Acad. Sci. USA 94, 10844–10849 (1997).

    Article  PubMed  CAS  Google Scholar 

  13. T. Shoham, R. Rajapaksa, C. Boucheix, E. Rubinstein, J. C. Poe, T. F. Tedder and S. Levy, The tetraspanin CD81 regulates the expression of CD19 during B cell development in a postendoplasmic reticulum compartment. J. Immunol. 171, 4062–4072 (2003).

    PubMed  CAS  Google Scholar 

  14. G. A. Deblandre, O. P. Marinx, S. S. Evans, S. Majjaj, O. Leo, D. Caput, G. A. Huez and M. G. Wathelet, Expression cloning of an interferon-inducible 17-kDa membrane protein implicated in the control of cell growth. J. Biol. Chem. 270, 23860–23866 (1995).

    Article  PubMed  CAS  Google Scholar 

  15. L. E. Bradbury, V. S. Goldmacher and T. F. Tedder, The CD19 signal transduction complex of B lymphocytes: deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu-13. J. Immunol. 151, 2915–2927 (1993).

    PubMed  CAS  Google Scholar 

  16. A. K. Matsumoto, D. R. Martin, R. H. Carter, L. B. Klickstein, J. M. Aheam and D. T. Fearon, Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. J. Exp. Med. 178, 1407–1417 (1993).

    Article  PubMed  CAS  Google Scholar 

  17. C. J. van Noesel, A. C. Lankester, G. M. van Schijndel and R. A. van Lier, The CR2/CD19 complex on human B cells contains the src-family kinase Lyn. Int. Immunol., 5, 699–705 (1993).

    Article  PubMed  Google Scholar 

  18. F._M. Uckun, A. L. Bukhardt, L. Jarvis, X. Jun, B. Stealey, I. Dibirdik, D. E. Myers, L. Tuel-Ahlgren and J. B. Bolen, Signal transduction through the CD19 receptor during discrete developmental stages of human B-cell ontogeny. J. Biol. Chem. 268, 21172–21184 (1993).

    PubMed  CAS  Google Scholar 

  19. N._J. Chalupny, S. B. Kanner, G. L. Schieven, S. Wee, L. K. Gilliland, A. Aruffo and J. A. Ledbetter, Tyrosine phosphorylation of CD19 in pre-B and mature B cells. EMBO J. 12, 2691–2696 (1993).

    PubMed  CAS  Google Scholar 

  20. M. Fujimoto, J. C. Poe, P. J. Jansen, S. Sato and T. F. Tedder CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation. J. Immunol. 162, 7088–7094 (1999).

    PubMed  CAS  Google Scholar 

  21. M. Fujimoto, Y. Fujimoto, J. C. Poe, P. J. Jansen, C. A. Lowell, A. L. DeFranco and T. F. Tedder, CD19 regulates Src-family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity 13, 47–57 (2000).

    Article  PubMed  CAS  Google Scholar 

  22. M. Hasegawa, M. Fujimoto, J. C. Poe, D. A. Steeber, C. A. Lowell and T. F. Tedder, A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice. J. Immunol. 167, 2469–2478 (2001).

    PubMed  CAS  Google Scholar 

  23. M. Fujimoto, J. C. Poe, M. Inaoki and T. F. Tedder, CD19 regulates B lymphocyte responses to transmembrane signals. Semin. Immunol. 10, 267–277 (1998).

    Article  PubMed  CAS  Google Scholar 

  24. P. A. Zipfel, M. Grove, K. Blackburn, M. Fujimoto, T. F. Tedder and A. M. Pendergast, The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19. J. Immunol. 165, 6872–6879 (2000).

    PubMed  CAS  Google Scholar 

  25. A. Cherukuri, P. C. Cheng, H. W. Sohn and S. K. Pierce, The CD19/CD21 complex functions to prolong B cell antigen receptor signaling from lipid rafts. Immunity 14, 169–179 (2001).

    Article  PubMed  CAS  Google Scholar 

  26. M. Fujimoto, A. P. Bradney, J. C. Poe, D. A. Steeber and T. F. Tedder, Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop. Immunity 11, 191–200 (1999).

    Article  PubMed  CAS  Google Scholar 

  27. S. Sato, P. J. Jansen and T. F. Tedder, CD19 and CD22 reciprocally regulate Vav tyrosine phosphorylation during B lymphocyte signaling. Proc. Natl. Acad. Sci., USA 94, 13158–13162 (1997).

    Article  PubMed  CAS  Google Scholar 

  28. W. K. Weng, L. Jarvis and T. W. LeBien, Signaling through CD19 activates vav/mitogen-activated protein kinase pathway and induces formation of a Cd19/vav/phosphatidylinositol 3-kinase complex in human B cell precursors. J. Biol. Chem. 269, 32514–32521 (1994).

    PubMed  CAS  Google Scholar 

  29. D. A. Tuveson, R. H. Carter, S. P. Soltoff and D. T. Fearon, CD19 of B cells as a surrogate kinase insert region to bind phosphatidylinositol 3-kinase. Science 260, 986–989 (1993).

    Article  PubMed  CAS  Google Scholar 

  30. A. M. Buhl, C. M. Pleiman, R. C. Rickert and J. C., Qualitative regulation of B cell antigen receptor signaling by CD19: Selective requirement for P13-kinase activation, inositol-1,4,5-trisphosphate production and Ca2+ mobilization. J. Exp. Med. 186, 1897–1910 (1997).

    Article  PubMed  CAS  Google Scholar 

  31. G. M. Doody, D. D. Balladeau, E. Clayton, A. Hutchings, R. Berland, S. McAdam, P. J. Leibson and M. Turner, Vav-2 controls NFAT-dependent transcription in B-but not T-lymphocytes. EMBO J. 19, 6173–6184 (2000).

    Article  PubMed  CAS  Google Scholar 

  32. S. R. Brooks, X. Li, E. J. Volanakis and R. H. Carter, Systematic analysis of the role of CD19 cytoplasmic tyrosines in enhancement of activation in Dandi human B cells: clustering of phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines. J. Immunol. 164, 3123–3131 (2000).

    PubMed  CAS  Google Scholar 

  33. J. C. Poe, M. Fujimoto, P. J. Jansen, A. S. Miller and T. F. Tedder, CD22 forms a quatemary complex with SHIP, Grb2 and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux. J. Biol. Chem. 275, 17420–17427 (2000).

    Article  PubMed  CAS  Google Scholar 

  34. R. H. Carter and D. T. Fearon, CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256, 105–107 (1992).

    Article  PubMed  CAS  Google Scholar 

  35. P. W. Dempsey, M. E. D. Allison, S. Akkaraju, C. C. Goodnow and D. T. Fearon, C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271, 348–350 (1996).

    Article  PubMed  CAS  Google Scholar 

  36. R. M. Tooze, G. M. Doody and D. T. Fearon, Counterregulation by the coreceptors CD19 and CD22 of MAP kinase activation by membrane immunoglobulin. Immunity 7, 59–67 (1997).

    Article  PubMed  CAS  Google Scholar 

  37. T. F. Tedder, M. Inaoki and S. Sato, The CD19/21 complex regulates signal transduction thresholds goveming humoral immunity and autoimmunity. Immunity 6, 107–118 (1997).

    Article  PubMed  CAS  Google Scholar 

  38. P. Engel, L.-J. Zhou, D. C. Ord, S. Sato, B. Koller and T. F. Tedder, Abnormal B lymphocyte development, activation and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3, 39–50 (1995).

    Article  PubMed  CAS  Google Scholar 

  39. L.-J. Zhou, H. M. Smith, T. J. Waldschmidt, R. Schwarting, J. Daley and T. F. Tedder, Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B lymphocyte development. Mol. Cell. Biol. 14, 3884–3894 (1994).

    PubMed  CAS  Google Scholar 

  40. R. C. Rickert, K. Rajewsky and J. Roes, Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature 376, 352–355 (1995).

    Article  PubMed  CAS  Google Scholar 

  41. S. Sato, D. A. Steeber and T. F. Tedder, The CD19 signal transduction molecule is a response regulator of B-lymphocyte differentiation. Proc. Natl. Acad. Sci. USA 92, 11558–11562 (1995).

    Article  PubMed  CAS  Google Scholar 

  42. S. Sato, A. S. Miller, M. C. Howard and T. F. Tedder, Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19. J. Immunol. 159, 3278–3287 (1997).

    PubMed  CAS  Google Scholar 

  43. A. Pezzutto, B. Dorken, P. S. Rabinovitch, J. A. Ledbetter, G. Moldenhauer and E. A. Clark, CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J. Immunol. 138, 2793–2799 (1987).

    PubMed  CAS  Google Scholar 

  44. T. B. Barrett, G. L. Shu, K. E. Draves, A. Pezzutto and E. A. Clark, Signaling through CD19, Fc receptors or transforming growth factor-β: each inhibits the activation of resting human B cells differently. Eur. J. Immunol. 20, 1053–1059 (1990).

    Article  PubMed  CAS  Google Scholar 

  45. R. E. Callard, K. P. Rigley, S. H. Smith, S. Thurstan and J. G. Shields, CD19 regulation of human B cell responses, B cell proliferation and antibody secretion are inhibited or enhanced by ligation of the CD19 surface glycoprotein depending on the stimulating signal used. J. Immunol. 148, 2983–2987 (1992).

    PubMed  CAS  Google Scholar 

  46. D. T. Fearon and R. H. Carter, The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu. Rev. Immunol. 13, 127–149 (1995).

    Article  PubMed  CAS  Google Scholar 

  47. C. J. M. van Noesel, A. C. Lankester and R. A. W. van Lier, Dual antigen recognition by B cells. Immunol. Today 14, 8–11 (1993).

    Article  PubMed  Google Scholar 

  48. J. M. Ahearn, M. B. Fischer, D. Croix, S. Goerg, M. Ma, J. Xia, X. Zhou, R. G. Howard, T. L. Rothstein and M. C. Carroll, 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, 251–262 (1996).

    Article  PubMed  CAS  Google Scholar 

  49. H. Molina, V. M. Holers, B. Li, Y.-F. Fang, S. Mariathasan, J. Goellner, J. Strauss-Schoenberger, R. W. Karr and D. D. Chaplin, Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc. Natl. Acad. Sci. USA 93, 3357–3361 (1996).

    Article  PubMed  CAS  Google Scholar 

  50. M. Hasegawa, M. Fujimoto, J. C. Poe, D. A. Steeber and T. F. Tedder, CD19 can regulate B lymphocyte signal transduction independent of complement activation. J. Immunol. 167, 3190–3200 (2001).

    PubMed  CAS  Google Scholar 

  51. T. F. Tedder, L. T. Clement and M. D. Cooper Discontinuous expression of a membrane antigen (HB-7) during B lymphocyte differentiation. Tissue Antigens 24, 140–149 (1984).

    Article  PubMed  CAS  Google Scholar 

  52. K. Takahashi, Y. Kozono, T. J. Waldschmidt, D. Berthiaume, R. J. Quigg, A. Baron and V. M. Holers, Mouse complement receptors type 1 (CR1; Cd35) and type (CR2; CD21). Expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice. J. Immunol. 159, 1557–1569 (1997).

    PubMed  CAS  Google Scholar 

  53. H. Molina, T. Kinoshita, K. Inoue, J.-C. Carel and V. M. Holers, A molecular and immunochemical characterization of mouse CR2. Evidence for a single gene model of mouse complement receptors 1 and 2. J. Immunol. 145, 2974–2983 (1990).

    PubMed  CAS  Google Scholar 

  54. M. D. Moore, N. R. Cooper, B. F. Tack and G. R. Nemerow, Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes. Proc. Natl. Acad. Sci. USA. 84, 9194–9198. (1987).

    Article  PubMed  CAS  Google Scholar 

  55. J. J. Weis, D. T. Fearon, L. B. Klickstein, W. W. Wong, S. A. Richards, A. d. Kops, J. A. Smith and J. H. Weis, Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement. Proc. Natl. Acad. Sci. USA 83, 5639–5643. (1986).

    Article  PubMed  CAS  Google Scholar 

  56. J. C. Carel, B. L. Myones, B. Frazier and V. M. Holers, Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization and viral infection. J. Biol. Chem. 265, 12293–12297 (1990).

    PubMed  CAS  Google Scholar 

  57. D. T. Fearon and M. C. Carroll, Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu. Rev. Immunol. 18, 393–422 (2000).

    Article  PubMed  CAS  Google Scholar 

  58. J. M. Ahcarn and D. T. Fearon, Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). Adv. Immunol. 46, 183–219 (1989).

    Google Scholar 

  59. K. M. Haas, M. Hasegawa, D. A. Steeber, J. C. Poe, M. D. Zabel, C. B. Bock, D. R. Karp, D. E. Briles, J. H. Weis and T. F. Tedder, Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses. Immunity 17, 713–723 (2002).

    Article  PubMed  CAS  Google Scholar 

  60. Z. Chen, S. B. Koralov, M. Gendelman, M. C. Carroll and G. Kelsoe, Humoral immune responses in Cr2-/- Mice: Enhanced affinity maturation but impaired antibody persistence. J. Immunol. 164, 4522–4532 (2000).

    PubMed  CAS  Google Scholar 

  61. X. Wu, N. Jiang, Y. Fang, C. Xu, D. Mao, J. Singh, Y. Fu and H. Molina, Impaired affinity maturation in Cr2-/- mice is rescued by adjuvants without improvement in germinal center development. J. Immunol. 165, 3119–3127 (2000).

    PubMed  CAS  Google Scholar 

  62. A. W. Griffioen, G. T. Rijkers, P. Janssens-Korpela and B. J. Zegers, Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2. Infect. Immun. 59, 1839–1845. (1991).

    PubMed  CAS  Google Scholar 

  63. T. Manser, K. M. Tumas-Brundage, L. P. Casson, A. M. Giusti, S. Hande, E. Notidis and K. A. Vora, The roles of antibody variable region hypermutation and selection in the development of the memory B-cell compartment. Immunol. Rev. 162, 183–196 (1998).

    Article  PubMed  CAS  Google Scholar 

  64. J. Pryjma, J. H. Humphrey and G. G. Klaus, C3 activation and T-independent B cell stimulation. Nature 252, 505–506. (1974).

    Article  PubMed  CAS  Google Scholar 

  65. O. G. Pozdnyakova, H.K. Guttormsen, F. N. Lalani, M. C. Carroll and D. L. Kasper, Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3-and complement receptor 2-deficient mice. J Immunol. 170, 84–90. (2003).

    PubMed  CAS  Google Scholar 

  66. M. J. Peset Llopis, G. Harms, M. J. Hardonk and W. Timens, Human immune response to pneumococcal polysaccharides: complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells. J. Allergy Clin. Immunol. 97, 1015–1024 (1996).

    Article  PubMed  CAS  Google Scholar 

  67. R. Guinamard, M. Okigaki, J. Schlessinger and J. V. Ravetch, Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral responses. Nature Immunol. 1, 31–36 (2000).

    Article  CAS  Google Scholar 

  68. S. E. Henson, D. Smith, S. A. Boackle, V. M. Holers and D. R. Karp, Generation of recombinant human C3dg tetramers for the analysis of CD21 binding and function. J. Immunol. Methods 258, 97–109. (2001).

    Article  PubMed  CAS  Google Scholar 

  69. W. Timens, A. Boes, T. Rozeboom-Uiterwijk and S. Poppema, Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. J. Immunol. 143, 3200–3206. (1989).

    PubMed  CAS  Google Scholar 

  70. A. Cariappa, M. Tang, C. Parng, E. Nebelitskiy, M. Carroll, K. Georgopoulos and S. Pillai, The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity 14, 603–615. (2001).

    Article  PubMed  CAS  Google Scholar 

  71. J. E. Figueroa and P. Densen, Infectious diseases associated with complement deficiencies. Clin. Microbiol. Rev. 4, 359–395. (1991).

    PubMed  CAS  Google Scholar 

  72. L. A. Burman, R. Norrby and B. Trollfors, Invasive pneumococcal infections: incidence, predisposing factors, and prognosis. Rev. Infect. Dis. 7, 133–142. (1985).

    PubMed  CAS  Google Scholar 

  73. I. D. Riley and R. M. Douglas, An epidemiologic approach to pneumococcal disease. Rev. Infect. Dis. 3, 233–245. (1981).

    PubMed  CAS  Google Scholar 

  74. M. Botto and M. J. Walport, Hereditary deficiency of C3 in animals and humans. Int. Rev. Immunol. 10, 37–50 (1993).

    PubMed  CAS  Google Scholar 

  75. J. A. Winkelstein, The role of complement in the host’s defense against Streptococcus pneumoniae. Rev. Infect. Dis. 3, 289–298. (1981).

    PubMed  CAS  Google Scholar 

  76. E. J. Brown, S. W. Hosea, C. H. Hammer, C. G. Burch and M. M. Frank, A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia. J. Clin. Invest. 69, 85–98. (1982).

    PubMed  CAS  Google Scholar 

  77. G. J. Noet, S. L. Katz and P. J. Edelson, The role of C3 in mediating binding and ingestion of group B streptococcus serotype III by murine macrophages. Pediatr. Res. 30, 118–123. (1991).

    Google Scholar 

  78. M. S. Borzy, A. Gewurz, L. Wolff, D. Houghton and E. Lovrien, Inherited C3 deficiency with recurrent infections and glomerulonephritis. Am. J. Dis. Child. 142, 79–83. (1988).

    PubMed  CAS  Google Scholar 

  79. E. J. Brown, S. W. Hosea and M. M. Frank, The role of complement in the localization of pneumococci in the splanchnic reticuloendothelial system during experimental bacteremia. J. Immunol. 126, 2230–2235. (1981).

    PubMed  CAS  Google Scholar 

  80. A. Circolo, G. Garnier, W. Fukuda, X. Wang, T. Hidvegi, A. J. Szalai, D. E. Briles, J. E. Volanakis, R. A. Wetsel and H. R. Colten, Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Immunopharmacology 42, 135–149. (1999).

    Article  PubMed  CAS  Google Scholar 

  81. Y. Fang, C. Xu, Y.-X. Fu, V. M. Holers and H. Molina, Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response. J. Immunol. 160, 5273–5279 (1998).

    PubMed  CAS  Google Scholar 

  82. J. Arvieux, H. Yssel and M. G. Colomb, Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones. Immunology 65, 229–235. (1988).

    PubMed  CAS  Google Scholar 

  83. S. A. Boackle, V. M. Holers and D. R. Karp CD21 augments antigen presentation in immune individuals. Eur. J. Immunol. 27, 122–129 (1997).

    Article  PubMed  CAS  Google Scholar 

  84. S. A. Boackle, M. A. Morris, V. M. Holers and D. R. Karp, Complement opsonization is required for presentation of immune complexes by resting peripheral blood B cells. J. Immunol. 161, 6537–6543. (1998).

    PubMed  CAS  Google Scholar 

  85. B. P. Thornton, V. Vetvieka and G. D. Ross, Natural antibody and complement-mediated antigen processing and presentation by B lymphocytes. J. Immunol. 152, 1727–1737. (1994).

    PubMed  CAS  Google Scholar 

  86. A. Cherukuri, P. C. Cheng and S. K. Pierce, The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J. Immunol. 167, 163–172. (2001).

    PubMed  CAS  Google Scholar 

  87. F. Martin, A. M. Oliver and J. F. Keamey, Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14, 617–629. (2001).

    Article  PubMed  CAS  Google Scholar 

  88. A. M. Oliver, F. Martin and J. F. Kearney, IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells. J. Immunol. 162, 7198–7207 (1999).

    PubMed  CAS  Google Scholar 

  89. J. C. Poe, M. Hasegawa and T. F. Tedder, CD19, CD21 and CD22: multifaceted response regulators of B lymphocyte signal transduction. Int. Rev. Immunol. 20, 739–762 (2001).

    PubMed  CAS  Google Scholar 

  90. R. M. Perlmutter, D. Hansburg, D. E. Briles, R. A. Nicolotti and J. M. Davie, Subclass restriction of murine anti-carbohydrate antibodies. J. Immunol. 121, 566–572. (1978).

    PubMed  CAS  Google Scholar 

  91. J. McLay, E. Leonard, S. Petersen, D. Shapiro, N. S. Greenspan and J. R. Schreiber, Gamma-3 gene-distrupted mice selectively deficient in the dominant IgG subclass made to bacterial polysaccharides. II. Increased susceptibility to fatal pneumococcal sepsis due to absence of anti-polysaccharide IgG3 is corrected by induction of anti-polysaccharide IgG1. J. Immunol. 168, 3437–3443. (2002).

    PubMed  CAS  Google Scholar 

  92. D. E. Briles, W. H. Benjamin, Jr., W. J. Huster and B. Posey, Genetic approaches to the study of disease resistance: with special emphasis on the use of recombinant inbred mice. Curr. Top. Microbiol. Immunol. 124, 21–35 (1986).

    PubMed  CAS  Google Scholar 

  93. P. G. Shackelford, S. J. Nelson, A. T. Palma and M. H. Nahm, Human antibodies to group A streptococcal carbohydrate. Ontogeny, subclass restriction, and clonal diversity. J. Immunol. 140, 3200–3205. (1988).

    PubMed  CAS  Google Scholar 

  94. T. W. Kuijpers, R. S. Weening and T. A. Out, IgG subclass deficiencies and recurrent pyogenic infections: unresponsiveness against bacterial polysaccharide antigens. Allergol. Immunopathol. 20, 28–34, (1992).

    CAS  Google Scholar 

  95. N. S. Greenspan and L. J. Cooper, Cooperative binding by mouse IgG3 antibodies: implications for functional affinity, effector function, and isotype restriction. Springer Semin. Immunopathol. 15, 275–291 (1993).

    Article  PubMed  CAS  Google Scholar 

  96. H. Wardemann, T. Boehm, N. Dear and R. Carsetti, B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen. J. Exp. Med. 195, 771–780 (2002).

    Article  PubMed  CAS  Google Scholar 

  97. R. R. Hardy, C. E. Carmack, Y. S. Li and K. Hayakawa, Distinctive developmental origins and specificities of murine CD5+ B cells. Immunol. Rev. 137, 91–118 (1994).

    Article  PubMed  CAS  Google Scholar 

  98. T. M. Ross, Y. Xu, T. D. Green, D. C. Montefiori and H. L. Robinson, Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins. AIDS Res. and Human Retroviruses 17, 829–835 (2001).

    Article  CAS  Google Scholar 

  99. T. D. Green, D. C. Montefiori and T. M. Ross, Enhancement of antibodies to the human immunodeficiency virus type 1 envelope by using the molecular adjuvant C3d. J. Virology 77, 2046–2055 (2003).

    Article  PubMed  CAS  Google Scholar 

  100. J. A. Mitchell, T. D. Green, R. A. Bright and T. M. Ross, Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins. Vaccine 21, 902–914 (2003).

    Article  PubMed  CAS  Google Scholar 

  101. T. D. Green, B. R. Newton, P. Rota, Y. Xu, H. L. Robinson and T. M. Ross, Immune responses in mice to measles hemagglutin-C3d DNA vaccinations. Vaccine 20, 242–248 (2002).

    Article  Google Scholar 

  102. T. M. Ross, Y. Xu, R. A. Bright and H. L. Robinson, C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza challenge. Nature Immunol. 1, 127–131 (2000).

    Article  CAS  Google Scholar 

  103. I. Walanabe, T. M. Ross, S. I. Tamura, T. Ichinohe, S. Ito, H. Takahashi, H. Sawa, J. Chiba, T. Kurala, T. Sata and H. Hasegawa, Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin. Vaccine 21, 4532–4538. (2003).

    Article  CAS  Google Scholar 

  104. S. T. Test, J. Mitsuyoshi, C. C. Connolly and A. H. Lucas, Increased immunogenicity and induction of class switching by conjugation of complement C3d to pneumococcal serotype 14 capsular polysaccharide. Infect. Immun. 69, 3031–3040. (2001).

    Article  PubMed  CAS  Google Scholar 

  105. R. H. Carter, M. O. Spycher, Y. C. Ng, R. Hoffman and D. T. Fearon, Synergistic interaction between complement receptor type 2 and membrane IgM on B lymphocytes. J. Immunol. 141, 457–463 (1988).

    PubMed  CAS  Google Scholar 

  106. J. D. Fingeroth, M. A. Benedict, D. N. Levy and J. L. Strominger, Identification of murine complement receptor type 2. Proc. Natl. Acad. Sci. USA 86, 242–246 (1989).

    Article  PubMed  CAS  Google Scholar 

  107. K. M. Haas, F. R. Toapanta, J. A. Oliver, J. C. Poe, J. H. Weis, D. R. Karp, J. F. Bower, T. M. Ross and T. F. Tedder, C3d functions as a molecular adjuvant in the absence of CD21/35 expression. (submitted).

    Google Scholar 

  108. F. R. Vogel Improving vaccine performance with adjuvants. Clinical Infectious Diseases 30Suppl 3, S266–270 (2000).

    Article  PubMed  CAS  Google Scholar 

  109. M. Bennett and T. Leanderson, Was it there all the time? Scand. J. of Immunol. 57, 499–505 (2003).

    Article  CAS  Google Scholar 

  110. S. Sato, M. Hasegawa, M. Fujimoto, T. F. Tedder and K. Takehara, Quantitative genetic variation in CD19 expression correlates with autoimmunity in mice and humans. J. Immunol. 165, 6635–6643 (2000).

    PubMed  CAS  Google Scholar 

  111. Y. Okano Antinuclear antibody in systemic sclerosis (scleroderma). Rheum. Dis. Clin. North Am. 22, 709–735 (1996).

    Article  PubMed  CAS  Google Scholar 

  112. E. Saito, M. Fujimoto, M. Hasegawa, K. Komura, Y. Hamaguchi, Y. Kaburagi, T. Nagaoka, K. Takehara, T. F. Tedder and S. Sato, CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J. Clin. Invest 109, 1453–1462 (2002).

    Article  PubMed  CAS  Google Scholar 

  113. S. A. Boackle, V. M. Hoters, X. Chen, G. Szakonyi, D. R. Karp, E. K. Wakeland and L. Morel, Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15, 775–785. (2001).

    Article  PubMed  CAS  Google Scholar 

  114. A. P. Prodeus, S. Goerg, L. M. Shen, O. O. Pozdnyakova, L. Chu, E. M. Alicot, C. C. Goodnow and M. C. Carroll, A critical role for complement in maintenance of self-tolerance. Immunity 9, 721–731 (1998).

    Article  PubMed  CAS  Google Scholar 

  115. M. Carroll, The role of complement in B cell activation and tolerance. Adv. Immunol. 74, 61–88 (2000).

    Article  PubMed  CAS  Google Scholar 

  116. Z. Chen, S. B. Koralov and G. Kelsoe, Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2. J. Exp. Med. 192, 1339–1351 (2000).

    Article  PubMed  CAS  Google Scholar 

  117. J. P. Atkinson, in: Systemic Lupus Erythematosus. edited R. G. Lahita (Churehill Livingston, Edinburgh; 1992), pp. 87–102.

    Google Scholar 

  118. M. Fujimoto, J. C. Poe, M. Hasegawa and T. F. Tedder, CD19 amplification of B lymphocyte Ca2+ responses: A role for Lyn sequestration in extinguishing negative regulation. J. Biol. Chem. 276, 44820–44827 (2001).

    Article  PubMed  CAS  Google Scholar 

  119. L. Chakravarty, M. D. Zabel, J. J. Weis and J. H. Weis, Depletion of Lyn kinase from the BCR complex and inhibition of B cell activation by excess CD21 ligation. Intl. Immunol. 14, 139–146 (2002).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Duke University Medical Center, Durham, North Carolina, 27710

    Thomas F. Tedder

Authors
  1. Karen M. Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas F. Tedder
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California Irvine, Irvine, California

    Sudhir Gupta

  2. NIAID, NIH, Bethesda, Maryland

    William E. Paul

  3. Rockefeller University, New York, New York

    Ralph Steinman

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer Science + Business Media, Inc.

About this paper

Cite this paper

Haas, K.M., Tedder, T.F. (2005). Role of the CD19 and CD21/35 Receptor Complex in Innate Immunity, Host Defense and Autoimmunity. In: Gupta, S., Paul, W.E., Steinman, R. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation X. Advances in Experimental Medicine and Biology, vol 560. Springer, Boston, MA. https://doi.org/10.1007/0-387-24180-9_16

Download citation

Publish with us

Policies and ethics

Search

Navigation