Almaden, J. V. and Tsui, R. and Liu, Y. C. (2014) A Pathway Switch Directs BAFF Signaling to Distinct NF kappa B Transcription Factors in Maturing and Proliferating B Cells. Cell Reports, 9 (6). pp. 2098-2111.

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Abstract

BAFF, an activator of the noncanonical NF kappa B pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NF kappa 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 kappa Bsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of I kappa Bsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NF kappa B network states during B cell biology, which causes BAFF to have context-dependent functional consequences.

Item Type:	Article
Subjects:	Biochemistry and Structural Biology
Depositing User:	Unnamed user with email alok@urdip.res.in
Date Deposited:	31 Mar 2015 08:56
Last Modified:	31 Mar 2015 08:56
URI:	http://nii.sciencecentral.in/id/eprint/4

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