Immunity
Volume 26, Issue 2, 23 February 2007, Pages 205-213
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Article
Autoreactivity in Human IgG+ Memory B Cells

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Summary

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.

CELLIMMUNO
HUMDISEASE

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These authors contributed equally to this work.