Role of repetitive antigen patterns for induction of antibodies against antibodies

J Exp Med. 1997 May 19;185(10):1785-92. doi: 10.1084/jem.185.10.1785.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / biosynthesis*
  • Antibodies, Monoclonal
  • Antibody Formation
  • Autoantibodies / immunology*
  • Cell Line
  • Cricetinae
  • Epitopes / immunology*
  • Immunoglobulin Allotypes / immunology
  • Immunoglobulin Constant Regions / immunology
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin Idiotypes / immunology
  • Immunoglobulin M / immunology
  • Immunoglobulin Variable Region / immunology
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred BALB C
  • O Antigens / immunology
  • Pseudomonas aeruginosa / immunology
  • Recombinant Fusion Proteins / immunology
  • Vesicular stomatitis Indiana virus / immunology
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Autoantibodies
  • Epitopes
  • G protein, vesicular stomatitis virus
  • Immunoglobulin Allotypes
  • Immunoglobulin Constant Regions
  • Immunoglobulin G
  • Immunoglobulin Idiotypes
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Membrane Glycoproteins
  • O Antigens
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins