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. 1990 Dec 1;172(6):1861–1864. doi: 10.1084/jem.172.6.1861

CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells

PMCID: PMC2188752  PMID: 1701824

Abstract

A novel pathway of IgE-B cell differentiation has been identified. Engagement of the B cell antigen CD40 by F(ab')2 fragments of monoclonal antibody (mAb) 626.1 in the presence of recombinant interleukin 4 (rIL-4) induced intense IgE synthesis, but modest IgG synthesis, by highly purified human B cells. Surface IgE- B cells isolated by cell sorting were induced to produce IgE by mAb 626.1 and IL-4. Thus, IgE synthesis is unlikely to result from expansion of a B cell population precommitted to IgE in vivo. A neutralizing anti-IL-6 antibody strongly, but not completely, inhibited the IgE response. This indicates that autocrine production of IL-6 plays an important amplification role in IgE synthesis triggered by anti-CD40 mAb and IL- 4. Although the exact role played by CD40 in IgE responses in vivo remains to be established, this T cell-independent system represents a useful model to characterize the biochemical and molecular events leading to IgE synthesis in human B cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clark E. A., Shu G. L., Lüscher B., Draves K. E., Banchereau J., Ledbetter J. A., Valentine M. A. Activation of human B cells. Comparison of the signal transduced by IL-4 to four different competence signals. J Immunol. 1989 Dec 15;143(12):3873–3880. [PubMed] [Google Scholar]
  2. Clark E. A., Shu G. Association between IL-6 and CD40 signaling. IL-6 induces phosphorylation of CD40 receptors. J Immunol. 1990 Sep 1;145(5):1400–1406. [PubMed] [Google Scholar]
  3. Gauchat J. F., Lebman D. A., Coffman R. L., Gascan H., de Vries J. E. Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production. J Exp Med. 1990 Aug 1;172(2):463–473. doi: 10.1084/jem.172.2.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gerondakis S. Structure and expression of murine germ-line immunoglobulin epsilon heavy chain transcripts induced by interleukin 4. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1581–1585. doi: 10.1073/pnas.87.4.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gruber M. F., Bjorndahl J. M., Nakamura S., Fu S. M. Anti-CD45 inhibition of human B cell proliferation depends on the nature of activation signals and the state of B cell activation. A study with anti-IgM and anti-CDw40 antibodies. J Immunol. 1989 Jun 15;142(12):4144–4152. [PubMed] [Google Scholar]
  6. Ledbetter J. A., Shu G., Gallagher M., Clark E. A. Augmentation of normal and malignant B cell proliferation by monoclonal antibody to the B cell-specific antigen BP50 (CDW40). J Immunol. 1987 Feb 1;138(3):788–794. [PubMed] [Google Scholar]
  7. MacKenzie T., Dosch H. M. Clonal and molecular characteristics of the human IgE-committed B cell subset. J Exp Med. 1989 Feb 1;169(2):407–430. doi: 10.1084/jem.169.2.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Raynal M. C., Liu Z. Y., Hirano T., Mayer L., Kishimoto T., Chen-Kiang S. Interleukin 6 induces secretion of IgG1 by coordinated transcriptional activation and differential mRNA accumulation. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8024–8028. doi: 10.1073/pnas.86.20.8024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Smeland E. B., Blomhoff H. K., Funderud S., Shalaby M. R., Espevik T. Interleukin 4 induces selective production of interleukin 6 from normal human B lymphocytes. J Exp Med. 1989 Oct 1;170(4):1463–1468. doi: 10.1084/jem.170.4.1463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Smith C. A., Davis T., Anderson D., Solam L., Beckmann M. P., Jerzy R., Dower S. K., Cosman D., Goodwin R. G. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019–1023. doi: 10.1126/science.2160731. [DOI] [PubMed] [Google Scholar]
  11. Stamenkovic I., Clark E. A., Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J. 1989 May;8(5):1403–1410. doi: 10.1002/j.1460-2075.1989.tb03521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Thyphronitis G., Tsokos G. C., June C. H., Levine A. D., Finkelman F. D. IgE secretion by Epstein-Barr virus-infected purified human B lymphocytes is stimulated by interleukin 4 and suppressed by interferon gamma. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5580–5584. doi: 10.1073/pnas.86.14.5580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Tsokos G. C., Lambris J. D., Finkelman F. D., Anastassiou E. D., June C. H. Monovalent ligands of complement receptor 2 inhibit whereas polyvalent ligands enhance anti-Ig-induced human B cell intracytoplasmic free calcium concentration. J Immunol. 1990 Mar 1;144(5):1640–1645. [PubMed] [Google Scholar]
  14. Vercelli D., Geha R. S. Regulation of IgE synthesis in humans. J Clin Immunol. 1989 Mar;9(2):75–83. doi: 10.1007/BF00916934. [DOI] [PubMed] [Google Scholar]
  15. Vercelli D., Jabara H. H., Arai K., Geha R. S. Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens. J Exp Med. 1989 Apr 1;169(4):1295–1307. doi: 10.1084/jem.169.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vercelli D., Jabara H. H., Arai K., Yokota T., Geha R. S. Endogenous interleukin 6 plays an obligatory role in interleukin 4-dependent human IgE synthesis. Eur J Immunol. 1989 Aug;19(8):1419–1424. doi: 10.1002/eji.1830190811. [DOI] [PubMed] [Google Scholar]
  17. Vercelli D., Jabara H. H., Cunningham-Rundles C., Abrams J. S., Lewis D. B., Meyer J., Schneider L. C., Leung D. Y., Geha R. S. Regulation of immunoglobulin (Ig)E synthesis in the hyper-IgE syndrome. J Clin Invest. 1990 May;85(5):1666–1671. doi: 10.1172/JCI114618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Vercelli D., Jabara H. H., Lauener R. P., Geha R. S. IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures. J Immunol. 1990 Jan 15;144(2):570–573. [PubMed] [Google Scholar]

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