Autoreactivity in human IgG+ memory B cells

Immunity. 2007 Feb;26(2):205-13. doi: 10.1016/j.immuni.2007.01.009.


More than half of the nascent B cells in humans initially express autoreactive antibodies. However, most of these autoantibodies are removed from the repertoire at two checkpoints before maturation into naive B cells. A third checkpoint excludes remaining autoantibodies from the antigen-experienced IgM(+) memory B cell pool. Nevertheless, low-affinity self-reactive antibodies are frequently found in the serum of normal humans. To determine the source of these antibodies, we cloned and expressed antibodies from circulating human IgG(+) memory B cells. Surprisingly, we found that self-reactive antibodies including anti-nuclear antibodies were frequently expressed by IgG(+) memory B cells in healthy donors. Most of these antibodies were created de novo by somatic hypermutation during the transition between mature naive and IgG(+) memory B cells. We conclude that deregulation of self-reactive IgG(+) memory B cells may be associated with autoimmunity.

Publication types

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

MeSH terms

  • Antibody Affinity
  • Autoantibodies / analysis
  • Autoantibodies / immunology*
  • Autoimmunity / immunology*
  • B-Lymphocytes / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunologic Memory*
  • Polymerase Chain Reaction
  • Somatic Hypermutation, Immunoglobulin


  • Autoantibodies