Class switch recombination in B lymphopoiesis: a potential pathway for B cell autoimmunity

Autoimmun Rev. 2004 Aug;3(6):464-9. doi: 10.1016/j.autrev.2004.03.008.

Abstract

Pathogenic autoantibodies detected in autoimmune diseases are predominantly IgG isotypes, reflecting the generation and activation of an autoimmune memory B cell repertoire. It is not completely understood how such autoreactive cells are generated and escape central and/or peripheral tolerance mechanisms, and several models to explain this have been proposed. It is generally thought that B lymphocytes utilize IgM receptors for development and tolerance establishment, whereas IgG receptors are primarily used to promote memory formation and signal for memory-type responses. In here we review recent findings suggesting that spontaneously occurring class switch recombination in B lymphopoiesis confer B lymphocytes with a novel developmental pathway that is driven by non-IgM receptors. The physiological relevance of this developmental pathway in generating an autoimmune memory repertoire, as well as a Fas-dependent mechanism regulating it, is discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • B-Lymphocytes / immunology*
  • Humans
  • Immunoglobulin Class Switching*
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Lymphopoiesis / immunology*
  • fas Receptor / immunology

Substances

  • Immunoglobulin G
  • Immunoglobulin M
  • fas Receptor