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 Article
| Authors: | Hatada, E. N.; Do, R. K. G.; Orlofsky, A.; Liou, H. C.; Prystowsky, M.; MacLennan, I. C. M.; Caamano, J.; Chen-Kiang, S. |
| Article Title: | 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 |
| 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. |
| Keywords: | signal transduction; protein phosphorylation; unclassified drug; nonhuman; protein analysis; animal cell; mouse; animals; mice; mice, knockout; cell survival; complex formation; apoptosis; proteasome; cell maturation; protein; membrane proteins; immunoglobulin enhancer binding protein; cell differentiation; transcription factor rela; bcl-x protein; phosphorylation; mice, inbred c57bl; b lymphocyte; dna; protein processing; protein processing, post-translational; tumor necrosis factor-alpha; protein synthesis; nf-kappa b; cell isolation; immunoblotting; protein biosynthesis; up-regulation; dna binding; proto-oncogene proteins c-bcl-2; synaptotagmin; tumor necrosis factor; i kappa b; interphase; i-kappa b proteins; protein p50; protein p52; cell kinetics; b-cell activating factor; priority journal; article; b-lymphocyte subsets; protein blys; protein p100; ribonuclease protection assay; nf-kappa b p50 subunit; nf-kappa b p52 subunit |
| Journal Title: | Journal of Immunology |
| Volume: | 171 |
| Issue: | 2 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2003-07-01 |
| Start Page: | 761 |
| End Page: | 768 |
| Language: | English |
| PUBMED: | 12847243 |
| PROVIDER: | scopus |
| DOI: | 10.4049/jimmunol.171.2.761 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
