The Journal of Experimental Medicine
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Published online 6 March 2006 doi:10.1084/jem.20051407
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 731-741
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ARTICLE

 Loss of the proapoptotic protein, Bim, breaks B cell anergy

Paula M. Oliver1,2, Tibor Vass1, John Kappler1,2,3,4, and Philippa Marrack1,2,3,5

1 Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, 2 Department of Immunology, 3 Department of Medicine, 4 Department of Pharmacology, and 5 Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80206

CORRESPONDENCE Philippa Marrack: marrackp{at}njc.org

Although B cells that respond with high avidity to self-antigen are eliminated early in their development, many autoreactive B cells escape elimination and are tolerized later in their lives via anergy. Anergic B cells are unresponsive to antigen and die prematurely. It has been suggested that the proapoptotic protein, Bim, controls the fate of anergic B cells. To test this idea, mice lacking Bim were crossed with mice that express soluble hen egg lysozyme and whose B cells bear receptors specific for the protein. In Bim+/+ mice these B cells are anergic and die rapidly. If the mice lack Bim, however, the B cells live longer, are more mature, respond to antigen, and secrete anti–hen egg lysozyme antibodies. This break of tolerance is not due to expression of endogenous B cell receptors, nor is it dependent on T cells. Rather, it appears to be due to a reduced requirement for the cytokine BAFF. Normal B cells require BAFF both for differentiation and survival. Bim–/– B cells, on the other hand, require BAFF only for differentiation. Therefore, autoreactive B cells are allowed to survive if they lack Bim and thus accumulate sufficient signals from differentiating factors to drive their maturation and production of autoantibodies.

Abbreviations used: BCR, B cell receptor; Dbl Tg, double transgenic; FO, follicular; HRP, horseradish peroxidase; MZ, marginal zone; sHEL, soluble hen egg lysozyme; T2, transitional 2.


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