Skip to main content

Advertisement

SpringerLink
Log in

The immunomodulatory effects of interferon-gamma on mature B-lymphocyte responses

  • Multi-author Review
  • Recent Developments in Interferon Research
  • Published:
Experientia Aims and scope Submit manuscript

Summary

Interferon-gamma (IFN-γ) exerts a broad spectrum of activities which affect the responses of mature B-cells. It strongly inhibits B-cell activation, acts as a B-cell growth factor (BCGF), and also induces final differentiation to immunoglobulin (Ig) production. IFN-γ is deeply involved in the differential control of isotype expression, as it enhances IgG2a production and suppresses both IgG1 and IgE production. Although it is now possible to draw a general scheme of the effects of IFN-γ on B-cells, a number of paradoxical results still exist in the field. In this manuscript, different experimental systems are analyzed in an attempt to explain these apparent paradoxes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alderson, M. R., Pike, B. L., and Nossal, G. J. V., Single cell studies on the role of B-cell stimulatory factor 1 in B-cell activation. Proc. natl Acad. Sci. USA84 (1987) 1389–1393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bijsterbosch, M. K., Meade, C. J., Turner, G. A., and Klaus, G. B. B., Lymphocyte receptors and polyphosphoinositide degradation. Cell41 (1985) 999–1006.

    Article  CAS  PubMed  Google Scholar 

  3. Bich-Thuy, L., and Fauci, A. S., Recombinant interleukin-2 and gamma interferon act synergistically on distinct steps of in vitro terminal human B cell maturation. J. clin. Invest. Inc.77 (1986) 1173–1179.

    Article  CAS  Google Scholar 

  4. Booth, R. J., Prestidge, R. L., and Watson, J. D., Interleukin 1 and B cell responsiveness. Lymphokines, 12. Ed. E. Pick. Academic Press New York.

  5. Coffman, R. L., Seymour, W. P., Lebman, D. A., Hiraki, D. D., Christiansen, J. A., Shrader, B., Cherwinski, H. M., Savelkoul, H. F. J., Finkelman, F. D., Bond, M. W., and Mosman, T. R., The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immun. Rev.102 (1988) 5–28.

    Article  CAS  PubMed  Google Scholar 

  6. DeFrance, T., Aubry, J.-P., Vanhervliet, B., and Banchereau, J., Human interferon-gamma acts as a B cell growth factor in the anti-IgM antibody co-stimulatory assay but has no direct B cell differentiation activity. J. Immun.137 (1986) 3861–3867.

    Article  CAS  PubMed  Google Scholar 

  7. Dugas, B., Calenda, A., Delfraissy, J.-F., Vazquez, A., Bach, J.-F., and Galanaud, P., The cytolsolic-free calcium in anti-μ-stimulated human B cells is derived partly from extracellular medium and partly from intracellular stores. Eur. J. Immun.17 (1987) 1323–1328.

    Article  CAS  Google Scholar 

  8. Dijkema, R., van der Meide, P. H., Pouwels, P. H., Caspers, M., Dubbeld, M., and Schellekens, H., Cloning and expression of the chromosomal immune interferon gene of the rat. EMBO J.4 (1985) 761–767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Finkelman, F. D., Katona, I. M., Mosmann, T. R., and Coffman, R. L., Interferon-gamma regulates the isotypes of immunoglobulin secreted during in vivo humoral imune responses. J. Immun.140 (1988) 1022–1027.

    Article  CAS  PubMed  Google Scholar 

  10. Gray, P. W., Leung, D. W., Pennica, D., Yelverton, E., Najarian, R., Simenson, C., Derynck, R., Sherwood, P. J., Wallas, D. M., Berger, S. L., Levinson, A. D., and Goeddel, D. V., Expression of human immune interferon cDNA inE. coli and monkey cells. Nature295 (1982) 503–508.

    Article  CAS  PubMed  Google Scholar 

  11. Gray, P. W., and Goeddel, D. V., Cloning and expression of murine interferon cDNA. Proc. natl Acad. Sci. USA80 (1983) 5842–5846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hoffmann, M. K., An alternate B cell activation mechanism mediated by macrophages through the release of cyclo-oxygenase pathway-products and interleukin 1. Lymphokine Res.6 (1987) 299–308.

    CAS  PubMed  Google Scholar 

  13. Jelinek, D. F., Splawski, B., and Lipsky, P. E., The roles of interleukin 2 and interferon-gamma in human B cell activation, growth and differentiation. Eur. J. Immun.16 (1986) 925–932.

    Article  CAS  Google Scholar 

  14. Jelinek, D. F., and Lipsy, P. E., Regulation of human B lymphocyte activation, proliferation, and differentiation. Adv. Immun.40 (1987) 1–23.

    Article  CAS  PubMed  Google Scholar 

  15. Julius, M. H., Heusser, C., and Hartmann, K. V., Induction of resting B cells to DNA synthesis by soluble monoclonal anti-immunoglobulin. Eur. J. Immun.14 (1984) 753–757.

    Article  CAS  Google Scholar 

  16. Leibson, H. J., Gefter, M., Zlotnik, A., Marrack, P., and Kappler, J. W., Role of gamma-interferon in antibody-producing responses. Nature309 (1984) 799–801.

    Article  CAS  PubMed  Google Scholar 

  17. Lin, S L., Kikuchi, T., Pledger, W. J., and Tamm, I., Interferon inhibits the establishment of competence in Go/S-phase transition. Science233 (1986) 356–359.

    Article  CAS  PubMed  Google Scholar 

  18. Mond, J. J., Finkelman, F. D., Sarma, C., Ohara, J., and Serrate, S., Recombinant interferon-gamma inhibits the B cell proliferative response stimulated by soluble but not by Sepharose-bound anti-immunoglobulin antibody. J. Immun.135 (1985) 2513–2517.

    Article  CAS  PubMed  Google Scholar 

  19. Mond, J. J., Carman, J., Sarma, C., Ohara, J., and Finkelman, F. D., Interferon-gamma suppresses B cell stimulation factor 1 (BSF-1) induction of class II MJC determinants on B cells. J. Immun.137 (1986) 3534–3537.

    Article  CAS  PubMed  Google Scholar 

  20. Nakagawa, T., Hirano, T., Nakagawa, N., Yoshizaki, K., and Kishimoto, T., Effect of recombinant IL 2 and gamma-IFN of proliferation and differentiation of human B cells. J. Immun.134 (1985) 959–966.

    Article  CAS  PubMed  Google Scholar 

  21. Nakagawa, T., Nakagawa, N., Volkman, D. J., and Fauci, A. S., Sequential synergistic effect of interleukin 2 and interferon-gamma on the differentiation of a Tac-antigen-postitive B cell line. J. Immun.136 (1986) 164–168.

    Article  CAS  PubMed  Google Scholar 

  22. Nakamura, M., Manser, T., Pearson, G. D. N., Daley, M. J., and Gefter, M., Effect of IFN-gamma on the immune response in vivo and on gene expression in vitro. Nature307 (1984) 381–382.

    Article  CAS  PubMed  Google Scholar 

  23. Nakanishi, K., Cohen, D. I., Blackman, M., Nielsen, E., Ohara, J., Hamaoka, T., Koshland, M. E., and Paul, W. E., Ig RNA expression in normal B cells stimulated with anti-IgM antibody and T cell-derived growth and differentiation factors. J. exp. Med.160 (1984) 1736–1751.

    Article  CAS  PubMed  Google Scholar 

  24. Noelle, R., Krammer, P. H., Ohara, J., and Uhr, J. W., Increased expression of Ia antigens on resting B cells: An additional role for B-cell growth factor. Proc. natl Acad. Sci. USA81 (1984) 6149–6153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. O'Garra, A., Rigley, K. P., Holman, M., McLaughlin, J. B., and Klaus, G. G. B., B-cell stimulatory factor 1 reverses Fc receptor-mediated inhibition of B-lymphocyte activation. Proc. natl Acad. Sci. USA84 (1987) 6254–6258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ohara, J., and Paul, W. E., Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature315 (1985) 333–336.

    Article  CAS  PubMed  Google Scholar 

  27. Petit-Koskas, E., Genot, E., Lawrence, D., and Kolb, J.-P., Inhibition of the proliferative response of human B lymphocytes to B cell growth factor by transforming growth factor beta. Eur. J. Immun.18 (1988) 111–116.

    Article  CAS  Google Scholar 

  28. Reynolds, D. S., Boom, W., Henry, A., and Abul, K., Inhibition of B lymphocyte activation by interferon-gamma. J. Immun.139 (1987) 767–773.

    Article  CAS  PubMed  Google Scholar 

  29. Roehms, N. W., Leibson, J. J., Zlotnik, A., Kappler, J. W., Marrack, P., and Cambier, J. C., Interleukin-induced increase in Ia expression by normal mouse B cells. J. exp. Med.160 (1984) 679–694.

    Article  Google Scholar 

  30. Romagnani, S., Giudizi, M. G., Biagiotti, R., Almerigogna, F., Mingari, C., Maggi, E., Liang, C.-M., and Moretta, L., B cell growth factor activity of interferon-gamma. Recombinant human interferongamma promotes proliferation of anti-μ activated human B lymphocytes. J. Immun.135 (1986) 3513–3516.

    Article  Google Scholar 

  31. Schimpl, A., and Wecker, E., Replacement of T cell function by a T cell product. Nature237 (1972) 15–18.

    CAS  Google Scholar 

  32. Sideras, P., Bergsted-Lindqvist, S., MacDonald, H. R., and Severinson, E., Secretion of IgG1 induction factor by T cell clones and hybridomas. Eur. J. Immun.15 (1985) 586–593.

    Article  CAS  Google Scholar 

  33. Sidman, C. L., Marshall, J. D., Shultz, L. D., Gray, P. W., and Johnson, H. M., Gamma-interferon is one of several direct B cell-maturing lymphokines. Nature309 (1984) 801–804.

    Article  CAS  PubMed  Google Scholar 

  34. Sidman, C. L., Marshall, J. D., Masiello, N. C., Roths, J. B., and Shultz, L. D., Novel B-cell maturation factor from spontaneously autoimmune viable motheaten mice. Proc. natl Acad. Sci. USA81 (1984) 7199–7202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sidman, C. L., Paige, C. J., and Schreier, M. H., B cell maturation factor (BMF): a lymphokine or a family of lympokines promoting the maturation of B lymphocytes. J. Immun.132 (1984) 209–222.

    Article  CAS  PubMed  Google Scholar 

  36. Snapper, C. M., and Paul, W. E., Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science236 (1987) 944–947.

    Article  CAS  PubMed  Google Scholar 

  37. Snapper, C. M., Finkelman, F. D., and Paul, W. E., Regulation of IgG1 and IgE production by interleukin 4. Immun. Rev.102 (1988) 51–75.

    Article  CAS  PubMed  Google Scholar 

  38. Snapper, C. M., Peschel, C., and Paul, W. E., Interferon-gamma stimulates IgG2a secretion by murine B cells stimulated with bacterial lipopolysaccharide. J. Immun.140 (1988) 2121–2127.

    Article  CAS  PubMed  Google Scholar 

  39. Vitetta, E. S., Brooks, K., Chen, Y-W., Isakson, P., Jones, S., Layton, J., Mishra, G. C., Pure, E., Weiss, E., Weiss, E., Word, C., Yuan, D., Tucker, P., Uhr, J. W., and Krammer, P. H., T cell derived lymphokines that induce IgM and IgG secretion inactivated murine B cells. Immun. Rev.78 (1984) 137–157.

    Article  CAS  PubMed  Google Scholar 

  40. Vitetta, E. S., Ohara, J., Myers, C. D., Layton, J. E., Krammer, P. H., and Paul, W. E., Serological, biochemical, and functional identity of B cell-stimulatory factor-1 and B cell differentiation factor for IgG1. J. exp. Med.162 (1985) 1726–1731.

    Article  CAS  PubMed  Google Scholar 

  41. Van Damme, J., Opdenakker, G., Simpson, R. J., Rubira, M. R., Cayphas, S., Vink, A., Billau, A., and Van Snick, J., Identification of the human 26-kD protein, interferon beta 2 (IFNB 2) as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J. exp. Med.165 (1987) 914–919.

    Article  PubMed  Google Scholar 

  42. Wilson, H. A., Greenblatt, D., Poenie, M., Finkelman, F. D., and Tsien, R. Y., Crosslinkage of B lymphocyte surface immunoglobulin by anti-Ig or antigen induces prolonged oscillation of intracellular ionized calcium. J. exp. Med.166 (1987) 601–606.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Veterinary Infectious Disease Organization, S7NOWO, Saskatoon, Saskatchewan, Canada

    A. Jurado

  2. Swiss Institute of Allergy and Asthma Research, CH-7270, Davos, Switzerland

    J. Carballido

  3. Ciba-Geigy, Pharmaceutical Research, CH-4002, Basel, Switzerland

    H. Griffel & H. K. Hochkeppel

  4. Basel Institute of Immunology, CH-4005, Basel, Switzerland

    G. D. Wetzel

Authors
  1. A. Jurado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Carballido
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Griffel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. K. Hochkeppel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. D. Wetzel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jurado, A., Carballido, J., Griffel, H. et al. The immunomodulatory effects of interferon-gamma on mature B-lymphocyte responses. Experientia 45, 521–526 (1989). https://doi.org/10.1007/BF01990501

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01990501

Key words

Search

Navigation