Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [46 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-00327349
Contributor : Marie-Christine Vougny <>
Submitted on : Saturday, February 27, 2010 - 1:29:30 PM
Last modification on : Wednesday, October 14, 2020 - 3:57:11 AM
Long-term archiving on: : Monday, October 8, 2012 - 2:10:28 PM

File

Gaudin_2004.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

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.. The Journal of Experimental Medecine, The Rockefeller University Press, 2004, 199 (6), pp.843-53. ⟨10.1084/jem.20030955⟩. ⟨pasteur-00327349⟩

Share

Metrics

Record views

511

Files downloads

557