B cell receptor-mediated sustained c-Rel activation facilitates late transitional B cell survival through control of B cell activating factor receptor and NF-κB2

Iris Castro, Jacqueline A. Wright, Bazarragchaa Damdinsuren, Kristen L. Hoek, Gianluca Carlesso, Nicholas P. Shinners, Rachel M. Gerstein, Robert T. Woodland, Ranjan Sen, Wasif N. Khan

Research output: Contribution to journalArticle

Abstract

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; CD21int-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-κB2). 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-κB2, 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.

Original languageEnglish (US)
Pages (from-to)7729-7737
Number of pages9
JournalJournal of Immunology
Volume182
Issue number12
DOIs
StatePublished - Jun 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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    Castro, I., Wright, J. A., Damdinsuren, B., Hoek, K. L., Carlesso, G., Shinners, N. P., Gerstein, R. M., Woodland, R. T., Sen, R., & Khan, W. N. (2009). B cell receptor-mediated sustained c-Rel activation facilitates late transitional B cell survival through control of B cell activating factor receptor and NF-κB2. Journal of Immunology, 182(12), 7729-7737. https://doi.org/10.4049/jimmunol.0803281