B-cell tolerance checkpoints in health and autoimmunity

Curr Opin Immunol. 2008 Dec;20(6):632-8. doi: 10.1016/j.coi.2008.09.001. Epub 2008 Oct 25.


The enormous diversity of the antibody repertoire is generated by two mechanisms: recombination of immunoglobulin (Ig) gene variable (V), diversity (D), and joining (J) gene segments during the early stages of B-cell development in the bone marrow and somatic hypermutation (SHM) of functional Ig genes from antigen-activated B cells within secondary lymphoid organs. Diversity by V(D)J recombination and SHM not only provides protective humoral immunity but also generates potentially harmful clones expressing autoantibodies. Under normal circumstances, several mechanisms regulate the removal of autoreactive B cells and defects in central and peripheral B cell tolerance checkpoints are associated with the development of autoimmunity in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Autoantibodies / genetics
  • Autoantibodies / immunology
  • Autoimmunity / genetics
  • Autoimmunity / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Gene Rearrangement, B-Lymphocyte / immunology*
  • Humans
  • Immune Tolerance / immunology*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Recombination, Genetic / immunology*


  • Autoantibodies
  • Receptors, Antigen, B-Cell