Role of repetitive antigen patterns for induction of antibodies against antibodies.

Journal article

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.

Authors: Fehr, T; Bachmann, M; Bucher, E; Kalinke, U; Di Padova, F

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 185
• Issue: 10
• Pages: 1785-1792
• Publication date: 1997-05-01
• DOI: 10.1084/jem.185.10.1785
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Cell Line; Animals; O Antigens; Immunoglobulin M; Mice, Inbred BALB C; Mice; Autoantibodies; Antibodies, Monoclonal; Membrane Glycoproteins; Immunoglobulin Idiotypes; Pseudomonas aeruginosa; Immunoglobulin Allotypes; Vesicular stomatitis Indiana virus; Immunoglobulin Variable Region; Antibody Formation; Immunoglobulin Constant Regions; Cricetinae; Recombinant Fusion Proteins; Viral Envelope Proteins; Antibodies, Anti-Idiotypic; Epitopes; Immunoglobulin G