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

Cell Rep. 2014 Dec 24;9(6):2098-111. doi: 10.1016/j.celrep.2014.11.024. Epub 2014 Dec 11.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / physiology
  • Cell Differentiation
  • Cell Proliferation*
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Mice
  • Models, Biological
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Signal Transduction*


  • B-Cell Activating Factor
  • I-kappa B Proteins
  • NF-kappa B
  • Protein Subunits
  • Tnfsf13b protein, mouse

Associated data

  • GEO/GSE54588