Factors and Receptors Involved in the Selection of B Lymphocytes Responding to T-Dependent Antigen

  • J. Gordon
Conference paper


B lymphocyte responses to T-dependent (TD) antigens are characterized by a primary phase which tends to be restricted to the production of relatively low affinity antibodies of the immunoglobulin (Ig)M class and a secondary response where antibodies are of higher affinity and have switched to the use of downstream heavy chain genes. The so-called affinity maturation of TD responses has been attributed to a preference for preserving the better-fit antibodies available from the primary repertoire on secondary challenge or to recruitment de novo from a completely separate precursor pool. It is clear, however, that in contrast to the IgM antibody which dominates a primary challenge, switched antibodies from a secondary response exhibit an accumulation of mutations within the Ig variable regions.


Germinal Center CD40 Ligand Follicular Dendritic Cell Immunol Today Nerve Growth Factor Receptor 
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  1. Armitage RJ, Fanslow WC, Strockbine L et al. (1992) Molecular and biological characteri-zation of a murine ligand for CD40. Nature 357: 80–82PubMedCrossRefGoogle Scholar
  2. Aubry J-P, Pochon S, Graber P, Jansen KU, Bonnefoy J-Y (1992) CD21 is a ligand for CD23 and regulates IgE production. Nature 358: 505–507PubMedCrossRefGoogle Scholar
  3. Banchereau J, de Paoli P, Alie E, Garcia E, Rousset F (1991) Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science 251: 70–73PubMedCrossRefGoogle Scholar
  4. Bonnefoy J-Y, Henchoz S, Hardi D, Holder MJ, Gordon J. A subset of anti-CD21 antibodies promote the rescue of germinal center B cells from apoptosis. Eur J Immunol (in press)Google Scholar
  5. Casal P, Notkins AL (1989) CD5+ B lymphocytes, polyreactive antibodies, and the human B-cell repertoire. Immunol Today 10: 364–369CrossRefGoogle Scholar
  6. Clark EA, Ledbetter J A (1986) Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci USA 83: 4494–4498PubMedCrossRefGoogle Scholar
  7. Cooper NR, Moore MD, Nemerow GR (1988) Immunobiology of CR2, the B lymphocyte receptor for Epstein-Barr virus and the C3d fragment of complement. Annu Rev Immunol 6: 85–113PubMedCrossRefGoogle Scholar
  8. Delcayre AX, Salas F, Mathur S, Kovats K, Lotz M, Lernhardt W (1991) Epstein-Barr virus/complement receptor is an interferon a receptor. EMBO J 10: 919–926PubMedGoogle Scholar
  9. Gordon J (1992) Cytokine regulation of lymphopoeisis: implications for therapeutic strategies in lymphoma. Focus Growth Fact 3: 5–9Google Scholar
  10. Gordon J, Millsum M, Guy GR, Ledbetter JA (1987) Synergistic interaction between interleukin 4 and anti-Bp50 (CDw40) revealed in a novel B cell restimulation assay. Eur J Immunol 17: 1535–1538PubMedCrossRefGoogle Scholar
  11. Gordon J, Millsum M, Guy GR, Ledbetter J A (1988) Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. J Immunol 140: 1425–1430PubMedGoogle Scholar
  12. Gordon J, Millsum MJ, Flores–Romo L, Gillis S (1989a) Regulation of resting and cycling human B lymphocytes via surface IgM and the accessory molecules interleukin-4, CD23 and CD40. Immunology 68: 526–531Google Scholar
  13. Gordon J, Flores-Romo L, Cairns J A, Millsum M, Lane PJ, Johnson GD, MacLennan ICM (1989b) CD23: a multi-functional receptor/lymphokine? Immunol Today 10: 153–157PubMedCrossRefGoogle Scholar
  14. Gray D, Skarvall H (1988) B–cell memory is short–lived in the absence of antigen. Nature 336: 70–72PubMedCrossRefGoogle Scholar
  15. Gray D, Kosco M, Stockinger B (1991) Novel pathways of antigen presentation for the maintenance of memory. Int Immunol 3: 141–147PubMedCrossRefGoogle Scholar
  16. Holder MJ, Liu Y-J, Defrance T, Flores–Romo L, MacLennan ICM, Gordon J (1991) Growth factor requirements for the stimulation of germinal center B cells: evidence for an IL2–dependent pathway of development. Int Immunol 3: 1243–1251Google Scholar
  17. Holder M, Knox K, Gordon J (1992) Factors modifying survival pathways of germinal center B cells. Glucocorticoids and transforming growth factor-[3, but not cyclosporin A or anti-CD 19, block surface immunoglobulin–mediated rescue from apoptosis. Eur J Immunol 22: 2725–2728PubMedCrossRefGoogle Scholar
  18. Jacob J, Kelsoe G, Rajewsky K, Weiss U (1991) Intraclonal generation of antibody mutants in germinal centres. Nature 354: 389–391PubMedCrossRefGoogle Scholar
  19. Kantor AB (1991) The development and repertoire of B1 cells (CD5 B cells). Immunol Today 14: 389–392CrossRefGoogle Scholar
  20. Korsmeyer S (1992) Bcl–2: a repressor of lymphocyte death. Immunol Today 13: 285–288PubMedCrossRefGoogle Scholar
  21. Lederman S, Yellin MJ, Inghirami G, Lee JJ, Knowles DM, Chess L (1992) Molecular interactions mediating T–B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol 149: 3817–3826PubMedGoogle Scholar
  22. Liu Y-J, Joshua DE, Williams GT, Smith CA, Gordon J, MacLennan ICM (1989) Mechanism of antigen-driven selection in germinal centres. Nature 342: 929–931PubMedCrossRefGoogle Scholar
  23. Liu Y-J, Cairns JA, Holder MJ, Abbot SD, Jansen KU, Bonnefoy J-Y, Gordon J, MacLennan ICM (1991) Recombinant 25-kDa CD23 and interleukin la promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis. Eur J Immunol 21: 1107–1114PubMedCrossRefGoogle Scholar
  24. MacLennan ICM, Gray D (1986) Antigen–driven selection of virgin and memory B cells. Immunol Rev 91: 61–85Google Scholar
  25. Mallett S, Barclay AN (1991) A new superfamily of cell surface proteins related to the nerve growth factor receptor. Immunol Today 12: 220–223PubMedCrossRefGoogle Scholar
  26. Matsumoto AK, Kopicky-Burd J, Carter RH, Tuveson DA, Tedder TF, Fearon DT (1991) Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte containing CR2 and CD19. J Exp Med 175: 55–64CrossRefGoogle Scholar
  27. Paulie S, Ehlin-Henriksson B, Mellstedt H, Koho H, Ben-Aissa H, Perlmann P (1985) A p50 surface antigen restricted to human urinary bladder carcinomas and B lymphocytes. Cancer Immunol Immunother 20: 23–28PubMedCrossRefGoogle Scholar
  28. Stamenkovic I, Clark EA, Seed B (1989) A B–lymphocyte activation molecule related to nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J 8: 1403–1410PubMedGoogle Scholar
  29. UytdeHaag F, van der Heijden R, Osterhaus A (1991) Maintenance of immunological memory: a role for CD5+ B cells? Immunol Today 12: 439–442PubMedCrossRefGoogle Scholar
  30. Warner GL, Ludlow JW, Nelson DA, Scott DW (1992) Anti-immunoglobulin treatment of murine B-cell lymphomas induces active transforming growth factor but pRB hypo-phosphorylation is transforming growth factor independent. Cell Growth Differ 5: 175–181Google Scholar
  31. Wheeler K, Pound J, Gordon J, Jefferis R (1993) Engagement of CD40 lowers the threshold for activation of resting B cells via antigen receptor. Eur J Immunol 23: 1165–1168PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1994

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  • J. Gordon

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