Autoreactivity in Human IgG+ Memory B Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2007 Feb 20

PMID 17306569

Citations 246

Authors

Thomas Tiller

Makoto Tsuiji

Sergey Yurasov

Klara Velinzon

Michel C Nussenzweig

Hedda Wardemann

Affiliations

Soon will be listed here.

Abstract

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.

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