[HTML][HTML] Autoreactivity in human IgG+ memory B cells

T Tiller, M Tsuiji, S Yurasov, K Velinzon… - Immunity, 2007 - cell.com
T Tiller, M Tsuiji, S Yurasov, K Velinzon, MC Nussenzweig, H Wardemann
Immunity, 2007cell.com
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 …
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.
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