A pathway switch directs BAFF signaling to distinct NF?B transcription factors in maturing and proliferating B cells.

ABSTRACT: BAFF, an activator of the noncanonical NF?B pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NF?B family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric I?Bsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of I?Bsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NF?B network states during B cell biology, which causes BAFF to have context-dependent functional consequences.

SUBMITTER: Almaden JV 

PROVIDER: S-EPMC4889572 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature