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 B. Prystowsky, Ian C M MacLennan, Jorge Caamano, Selina Chen-Kiang

Research output: Contribution to journalArticle

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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
StatePublished - Jul 15 2003

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B-Cell Activating Factor
B-Lymphocytes
Apoptosis
Proteasome Endopeptidase Complex
Lymphocyte Activation
Genes
Proteins
Phosphorylation
DNA

ASJC Scopus subject areas

  • Immunology

Cite this

Hatada, E. N., Do, R. K. G., Orlofsky, A., Liou, H. C., Prystowsky, M. B., 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.

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

In: Journal of Immunology, Vol. 171, No. 2, 15.07.2003, p. 761-768.

Research output: Contribution to journalArticle

Hatada, EN, Do, RKG, Orlofsky, A, Liou, HC, Prystowsky, MB, MacLennan, ICM, Caamano, J & 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, vol. 171, no. 2, pp. 761-768.
Hatada, Eunice N. ; Do, Richard K G ; Orlofsky, Amos ; Liou, Hsiou Chi ; Prystowsky, Michael B. ; MacLennan, Ian C M ; Caamano, Jorge ; Chen-Kiang, Selina. / 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. In: Journal of Immunology. 2003 ; Vol. 171, No. 2. pp. 761-768.
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