title: Role of repetitive antigen patterns for induction of antibodies against antibodies.
abstract: 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.affiliation: Institute of Experimental Immunology, University of Zürich, CH-8091 Zürich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Fehr
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: E
authors.initials: E
authors.lastname: Bucher
authors.forename: U
authors.initials: U
authors.lastname: Kalinke
authors.forename: F E
authors.initials: FE
authors.lastname: Di Padova
authors.forename: A B
authors.initials: AB
authors.lastname: Lang
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D000939:Epitopes / Q000276:immunology*; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D019081:O Antigens / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; C028391:G protein, vesicular stomatitis virus; D007126:Immunoglobulin Allotypes; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D019081:O Antigens; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins