NF-κB1 p50 is required for BLyS attenuation of apoptosis but dispensable for processing of NF-κB2 p100 to p52 in quiescent mature B cells

Eunice N. Hatada, Richard K.G. Do, Amos Orlofsky, Hsiou Chi Liou, Michael Prystowsky, Ian C.M. MacLennan, Jorge Caamano, Selina Chen-Kiang

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Abstract

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-κB 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 IκBα characteristic of the classical NF-κB pathway, albeit maintaining IκBα 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-κB pathway. p50 is dispensable for p100 processing. However, it is required to mediate the initial BLyS survival signals and concomitant activation of Bcl-xL 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-κB pathways and selective downstream antiapoptotic genes.

Original languageEnglish (US)
Pages (from-to)761-768
Number of pages8
JournalJournal of Immunology
Volume171
Issue number2
Publication statusPublished - Jul 15 2003

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hatada, E. N., Do, R. K. G., Orlofsky, A., Liou, H. C., Prystowsky, M., MacLennan, I. C. M., ... Chen-Kiang, S. (2003). NF-κB1 p50 is required for BLyS attenuation of apoptosis but dispensable for processing of NF-κB2 p100 to p52 in quiescent mature B cells. Journal of Immunology, 171(2), 761-768.