Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Virus-induced autoantibody response to a transgenic viral antigen

Abstract

THE induction of autoantibodies and their possible role in the pathogenesis of autoimmune disease are poorly understood. Involvement of infectious agents has been suspected, but direct evidence is sparse1–4. Whether immunological unresponsiveness to self by antibody-forming ? cells is maintained by clonal abortion5, clonal anergy6–8 or suppression9, or how the scenario of interactions between helper T cells, B cells and antigen-presenting cells10,11–13 is distorted in autoantibody responses, is being analysed and widely debated3,6–8,14–17. To evaluate tolerance of neutralizing B-cell responses12,18 we used transgenic mice expressing the cell membrane associated glycoprotein (G) of vesicular stomatitis virus (VSV) as self-antigen. We show that autoantibodies to VSV-G cannot be induced by VSV-G in adjuvant or by recombinant vaccinia virus expressing VSV-G, but are triggered by infection with wild-type VSV. The data show that helper T-cell tolerance is crucial in maintenance of B-cell non-reactivity2,16,19,20 and that cognate T–B recognition is necessary to break tolerance of self-reactive B cells. These results may help to understand mechanisms of virus-induced autoimmunity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Talal, N. in Autoimmunity (ed. Talal, N.) 1–734 (Academic, San Francisco, 1977).

    Google Scholar 

  2. Weigle, W. O. Adv. Immun. 16, 61–122 (1973).

    Article  CAS  Google Scholar 

  3. Oldstone, M. B. A., Schwimmbeck, P., Dyrberg, T. & Fujinami, R. Prog. Immun. 6, 787–795 (1986).

    Article  Google Scholar 

  4. Mims, C. A. Pathogenesis of Infectious Disease (Academic, London, 1982).

    Google Scholar 

  5. Nemazee, D. A. & Bürki, K. Nature 337, 562–566 (1989).

    Article  ADS  CAS  Google Scholar 

  6. Nossal, G. J. V. Science 245, 147–153 (1989).

    Article  ADS  CAS  Google Scholar 

  7. Goodnow, C. C. et al. Nature 334, 676–682 (1988).

    Article  ADS  CAS  Google Scholar 

  8. DeFranco, A. L. Nature 342, 340–341 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Gershon, R. K. & Kondo, K. Immunology 18, 723–737 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Lanzavecchia, A. Curr. Top. Microbiol. Immun. 130, 65–78 (1986).

    CAS  Google Scholar 

  11. Mitchison, N. A. Eur. J. Immun. 1, 10–17 (1971).

    Article  CAS  Google Scholar 

  12. Zinkernagel, R. M., Rüedi, E., Althage, A., Hengartner, H. Reimann, G. J. exp. Med. 168, 1187–1192 (1988).

    Article  CAS  Google Scholar 

  13. Vercelli, D., Jabara, H. H., Arai, K. & Geha, R. S. J. exp. Med. 169, 1295–1307 (1989).

    Article  CAS  Google Scholar 

  14. Bretscher, P. Cell. Immun. 6, 1–11 (1973).

    Article  CAS  Google Scholar 

  15. Langman, R. E. The Immune System (Harcourt Brace Jovanovich, San Diego, 1989).

    Google Scholar 

  16. Mitchison, N. A. Proc. R. Soc. B161, 275–292 (1964).

    ADS  CAS  Google Scholar 

  17. Schwartz, R. H. Cell 57, 1073–1081 (1989).

    Article  CAS  Google Scholar 

  18. Gupta, S. C., Hengartner, H. & Zinkernagel, R. M. Proc. natn. Acad. Sci. U.S.A. 83, 2604–2608 (1986).

    Article  ADS  CAS  Google Scholar 

  19. Harris, D. E., Cairns, L., Rosen, F. S. & Borel, Y. J. exp. Med. 156, 567–584 (1982).

    Article  CAS  Google Scholar 

  20. Lake, P. & Mitchison, N. A. Cold Spring Harbor Symp. quant. Biol. 41, 589–595 (1977).

    Article  Google Scholar 

  21. Zinkernagel, R. M. & Rosenthal, K. L. Immunol. Rev. 58, 131–155 (1981).

    Article  CAS  Google Scholar 

  22. Yewdell, J. W. et al. J. exp. Med. 163, 1529–1538 (1986).

    Article  CAS  Google Scholar 

  23. Kelley, J. M., Emerson, S. U. & Wagner, R. R. J. Virol. 10, 1231–1235 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Lefrançois, L. & Lyles, D. S. Virology 121, 157–167 (1982).

    Article  Google Scholar 

  25. Mills, B. J., Beebe, D. P. & Cooper, N. R. J. Immun. 123, 2518–2524 (1979).

    CAS  PubMed  Google Scholar 

  26. Goodnow, C. C. Crosbie, J., Jörgensen, H., Brink, R. A. & Basten, A. Nature 342, 385–391 (1989).

    Article  ADS  CAS  Google Scholar 

  27. Gallione, C. & Rose, J. K. J. Virol. 46, 162–169 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. VandePol, S. B., Lefrançois, L. & Holland, J. J. Virology 148, 312–325 (1986).

    Article  CAS  Google Scholar 

  29. Karupiah, G. et al. J. Immun. 144, 290–298 (1990).

    CAS  PubMed  Google Scholar 

  30. Falke, D. & Rowe, W. P. Arch. ges. Virusforsch. 17, 549–559 (1965).

    Article  CAS  Google Scholar 

  31. Theofilopoulos, A. T. & Dixon, F. J. Adv. Immun. 28, 89–221 (1979).

    Article  CAS  Google Scholar 

  32. Möller, G. Immunol. Rev. 23, 126–137 (1975).

    Article  Google Scholar 

  33. Milich, D. R. Immun. Today 9, 380–386 (1988).

    Article  CAS  Google Scholar 

  34. Scherle, P. A. & Gerhard, W. J. exp. Med. 164, 1114–1128 (1986).

    Article  CAS  Google Scholar 

  35. Brett, S. J., Cease, K. B. & Berzofsky, J. A. J. exp. Med. 168, 357–373 (1988).

    Article  CAS  Google Scholar 

  36. Bodmer, H. C., Gotch, F. M. & McMichael, A. J. Nature 337, 653–655 (1989).

    Article  ADS  CAS  Google Scholar 

  37. Finnegan, A. & Amburgey, C. F. J. exp. Med. 170, 2171–2176 (1989).

    Article  CAS  Google Scholar 

  38. Carbone, F. R., Moore, M. W., Sheil, J. M. & Bevan, M. J. J. exp. Med. 167, 1767–1779 (1988).

    Article  CAS  Google Scholar 

  39. Rose, J. K. & Gallione, C. J. J. Virol. 39, 519–528 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Kenney, Sh., Natarajan, V., Strike, D., Khoury, G. & Salzman, N. P. Science 226, 1337–1339 (1984).

    Article  ADS  CAS  Google Scholar 

  41. Benoist, C. & Chambon, P. Nature 290, 304–310 (1981).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zinkernagel, R., Cooper, S., Chambers, J. et al. Virus-induced autoantibody response to a transgenic viral antigen. Nature 345, 68–71 (1990). https://doi.org/10.1038/345068a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/345068a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing