The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/5/1785/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 10, May 19, 1997 1785-1792

Articles

Role of Repetitive Antigen Patterns for Induction of Antibodies Against Antibodies

Thomas Fehr*, Martin F. Bachmann*, Etienne Bucher*, Ulrich Kalinke*, Franco E. Di Padova{ddagger}, Alois B. Lang§, Hans Hengartner*, and Rolf M. Zinkernagel*

From the * Institute of Experimental Immunology, University of Zürich, CH-8091 Zürich, Switzerland; {ddagger} Novartis Pharma AG, S-386.110, CH-4002 Basel, Switzerland; and the § Swiss Serum and Vaccine Institute, Department of Immunology, CH-3001 Bern, Switzerland

Antibody responses against antibodies, such as rheumatoid factors, are found in several immunopathological diseases and may play a role in disease pathogenesis. Experience shows that they are usually difficult to induce experimentally. Antibodies specific for immunoglobulin constant regions (anti-allotypic) or for variable regions (anti-idiotypic) have been investigated in animal models; the latter have even been postulated to regulate antibody and T cell responses via network-like interactions. Why and how such anti-antibodies are induced during autoimmune diseases, has remained largely unclear. Because repetitively arranged epitopes in a paracrystalline structure of a viral envelope cross-link B cell receptors efficiently to induce a prompt T-independent IgM response, this study used immune complexes containing viruses or bacteria to evaluate the role of antigen pattern for induction of anti-antibody responses. We present evidence that antibodies bound to strictly ordered, but not to irregularly arranged, antigens dramatically enhance induction of anti-antibodies, already after a single immunization and without using adjuvants. The results indicate a novel link between anti-antibody responses and infectious agents, and suggest a similar role for repetitive self-antigens such as DNA or collagen involved in chronic immunopathological diseases.

Address correspondence to R.M. Zinkernagel, Institute of Experimental Immunology, University of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland. Dr. Bachmann's present address is Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Canada M5G 2M9.

1 Abbreviations used in this paper: HRPO, horseradish peroxidase; IC, immune complex; P.a., Pseudomonas aeruginosa; RF, rheumatoid factors; S.t., Salmonella typhi; TS, trypic soy; VSV, vesicular stomatitis virus; VSV-G, VSV glycoprotein; VSV-G–huH{gamma}1, fusion protein of VSV-G with human IgG1 heavy chain constant regions; VSV-IND, VSV serotype Indiana; VSV-NJ, VSV serotype New Jersey.


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