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 Khan

Research output: Contribution to journalArticle

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

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Interleukin-4 Receptors
B-Lymphoid Precursor Cells
Cell Survival
B-Lymphocytes
Apoptosis
rel Genes
vpr Genes
Genes
Cell Differentiation

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

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. / 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.

In: Journal of Immunology, Vol. 182, No. 12, 15.06.2009, p. 7729-7737.

Research output: Contribution to journalArticle

Castro, I, Wright, JA, Damdinsuren, B, Hoek, KL, Carlesso, G, Shinners, NP, Gerstein, RM, Woodland, RT, Sen, R & Khan, W 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, vol. 182, no. 12, pp. 7729-7737. https://doi.org/10.4049/jimmunol.0803281
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. / 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. In: Journal of Immunology. 2009 ; Vol. 182, No. 12. pp. 7729-7737.
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