Journal
JOURNAL OF IMMUNOLOGY
Volume 171, Issue 2, Pages 761-768Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.2.761
Keywords
-
Categories
Funding
- NCI NIH HHS [CA80204] Funding Source: Medline
- NIAMS NIH HHS [AR49436] Funding Source: Medline
- NIGMS NIH HHS [GM07739] Funding Source: Medline
Ask authors/readers for more resources
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-kappaB 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 IkappaBalpha characteristic of the classical NF-kappaB pathway, albeit maintaining IkappaBalpha 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-kappaB pathway. p50 is dispensable for p100 processing. However, it is required to mediate the initial BLyS survival signals and concomitant activation of Bcl-x(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-kappaB pathways and selective downstream antiapoptotic genes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available