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. Academic Article uri icon

Overview

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-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.

publication date

  • July 15, 2003

Research

keywords

  • Apoptosis
  • B-Lymphocyte Subsets
  • Interphase
  • Membrane Proteins
  • NF-kappa B
  • Protein Processing, Post-Translational
  • Tumor Necrosis Factor-alpha

Identity

Scopus Document Identifier

  • 0038445996

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.171.2.761

PubMed ID

  • 12847243

Additional Document Info

volume

  • 171

issue

  • 2