B Cell Receptor-Mediated Sustained c-Rel Activation Facilitates Late Transitional B Cell Survival through Control of B Cell Activating Factor Receptor and NF-κB21

Signaling from the BCR and B cell activating factor receptor (BAFF-R or BR3) differentially regulates apoptosis within early transitional (T1) and late transitional (T2; CD21 int -T2) B cells during selection processes to generate mature B lymphocytes. However, molecular mechanisms underlying the di...

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Published in:The Journal of immunology (1950) 2009-06, Vol.182 (12), p.7729-7737
Main Authors: Castro, Iris, Wright, Jacqueline A., Damdinsuren, Bazarragchaa, Hoek, Kristen L., Carlesso, Gianluca, Shinners, Nicholas P., Gerstein, Rachel M., Woodland, Robert T., Sen, Ranjan, Khan, Wasif N.
Format: Article
Language:English
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Summary:Signaling from the BCR and B cell activating factor receptor (BAFF-R or BR3) differentially regulates apoptosis within early transitional (T1) and late transitional (T2; CD21 int -T2) B cells during selection processes to generate mature B lymphocytes. However, molecular mechanisms underlying the differential sensitivity of transitional B cells to apoptosis remain unclear. In this study, we demonstrate that BCR signaling induced more long-term c-Rel activation in T2 and mature than in T1 B cells leading to increased expression of anti-apoptotic genes as well as prosurvival BAFF-R and its downstream substrate p100 (NF- κ B2). Sustained c-Rel activation required de novo c- Rel gene transcription and translation via Btk-dependent mechanisms. Like T1 cells, mature B cells from Btk - and c- Rel -deficient mice also failed to activate these genes. These findings suggest that the gain of survival potential within transitional B cells is dependent on the ability to produce a long-term c-Rel response, which plays a critical role in T2 B cell survival and differentiation in vivo by inducing anti-apoptotic genes, BAFF-R and NF- κ B2, an essential component for BAFF-R survival signaling. Thus, acquisition of resistance to apoptosis during transitional B cell maturation is achieved by integration of BCR and BAFF-R signals.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0803281