Autoreactivity in human IgG+ memory B cells.
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.
Tiller
Thomas
T
Max-Planck-Institute for Infection Biology, D-10117 Berlin, Germany.
Tsuiji
Makoto
M
Yurasov
Sergey
S
Velinzon
Klara
K
Nussenzweig
Michel C
MC
Wardemann
Hedda
H
D000915:Antibody Affinity; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007156:Immunologic Memory; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin
D001323:Autoantibodies