期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 12, 页码 7729-7737出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803281
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资金
- National Institutes of Health [AI060729, AI041054, AI057463, AI043534, P30DK32520, DK32520, T32 HL69715-0, T32 CA09385-20, 5 T32 HL069765]
Signaling from the BCR anti 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 BC R signaling induced more long-term c-Rel activation in T2 anti 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-kappa 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 13 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-kappa 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. The Journal of Immunology, 2009, 182: 7729-7737.
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