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Positive selection of B cells expressing low densities of self-reactive BCRs.

Abstract : B cell tolerance or autoimmunity is determined by selective events. Negative selection of self-reactive B cells is well documented and proven. In contrast, positive selection of conventional B cells is yet to be firmly established. Here, we demonstrate that developing self-reactive B cells are not always highly sensitive to the deletion mechanisms imposed by membrane-bound self-antigens. At low amounts, membrane-bound antigens allow survival of B cells bearing a single high affinity self-reactive B cell receptor (BCR). More importantly, we show that forced allelic inclusion modifies B cell fate; low quantities of self-antigen induce the selection and accumulation of increased numbers of self-reactive B cells with decreased expression of antigen-specific BCRs. By directly measuring antigen binding by intact B cells, we show that the low amounts of self-antigen select self-reactive B cells with a lower association constant. A fraction of these B cells is activated and secretes autoantibodies that form circulating immune complexes with self-antigen. These findings demonstrate that conventional B cells can undergo positive selection and that the fate of a self-reactive B cell depends on the quantity of self-antigen, the number of BCRs engaged, and on its overall antigen-binding avidity, rather than on the affinity of individual BCRs.
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Contributor : Marie-Christine Vougny Connect in order to contact the contributor
Submitted on : Saturday, February 27, 2010 - 1:29:30 PM
Last modification on : Monday, October 17, 2022 - 1:28:59 PM
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Emmanuelle Gaudin, Yi Hao, Maria Manuela Rosado, Richard Chaby, Robert Girard, et al.. Positive selection of B cells expressing low densities of self-reactive BCRs.. Journal of Experimental Medicine, 2004, 199 (6), pp.843-53. ⟨10.1084/jem.20030955⟩. ⟨pasteur-00327349⟩



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