NF-{kappa}B1 p50 Is Required for BLyS Attenuation of Apoptosis but Dispensable for Processing of NF-{kappa}B2 p100 to p52 in Quiescent Mature B Cells

• Published in: The Journal of immunology (1950) 2003-07, Vol.171 (2), p.761-768
• Main Authors: Hatada, Eunice N, Do, Richard K. G, Orlofsky, Amos, Liou, Hsiou-Chi, Prystowsky, Michael, MacLennan, Ian C. M, Caamano, Jorge, Chen-Kiang, Selina
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

B lymphocyte stimulator (BLyS), a TNF family protein essential for peripheral B cell development, functions primarily through attenuation of B cell apoptosis. In this study, we show that BLyS activates NF-[kappa]B through both classical and alternative pathways with distinct kinetics in quiescent mature B cells. It rapidly and transiently enhances the p50/p65 DNA binding activity and induces phosphorylation of I[kappa]B[alpha] characteristic of the classical NF-[kappa]B pathway, albeit maintaining I[kappa]B[alpha] at a constant level through ongoing protein synthesis and proteasome-mediated destruction. With delayed kinetics, BLyS promotes the processing of p100 to p52 and sustained formation of p52/RelB complexes via the alternative NF-[kappa]B pathway. p50 is dispensable for p100 processing. However, it is required to mediate the initial BLyS survival signals and concomitant activation of Bcl-x sub(L) in quiescent mature B cells ex vivo. Although also a target of BLyS activation, at least one of the A1 genes, A1-a, is dispensable for the BLyS survival function. These results suggest that BLyS mediates its survival signals in metabolically restricted quiescent B cells, at least in part, through coordinated activation of both NF-[kappa]B pathways and selective downstream antiapoptotic genes.