B cells take the front seat: dysregulated B cell signals orchestrate loss of tolerance and autoantibody production

Curr Opin Immunol. 2015 Apr;33:70-7. doi: 10.1016/j.coi.2015.01.018. Epub 2015 Feb 11.

Abstract

A significant proportion of autoimmune-associated genetic variants are expressed in B cells, suggesting that B cells may play multiple roles in autoimmune pathogenesis. In this review, we highlight recent studies demonstrating that even modest alterations in B cell signaling are sufficient to promote autoimmunity. First, we describe several examples of genetic variations promoting B cell-intrinsic initiation of autoimmune germinal centers and autoantibody production. We highlight how dual antigen receptor/toll-like receptor signals greatly facilitate this process and how activated, self-reactive B cells may function as antigen presenting cells, leading to loss of T cell tolerance. Further, we propose that B cell-derived cytokines may initiate and/or sustain autoimmune germinal centers, likely also contributing, in parallel, to programing of self-reactive T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Autoantibodies / immunology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmunity / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cytokines / metabolism
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Humans
  • Immune Tolerance
  • Signal Transduction

Substances

  • Autoantibodies
  • Cytokines