B cell survival and development controlled by the coordination of NFκB family members RelB and cRel

Jonathan V. Almaden, Yi C. Liu, Edward Yang, Dennis Otero, Harry Birnbaum, Jeremy Davis-Turak, Masataka Asagiri, Michael David, Ananda W. Goldrath and Alexander Hoffmann

Key points

  • NFκB family members RelB and cRel are coordinately activated by BAFF and provide distinct survival signals.

  • In vivo and in vitro B cell developmental defects are observed when both RelB and cRel are deleted.


Targeted deletion of BAFF causes severe deficiency of splenic B cells. BAFF-R is commonly thought to signal to NIK-dependent non-canonical NFκB RelB. However, RelB-deficient mice have normal B cell numbers. Recent studies showed that BAFF also signals to the canonical NFκB pathway, and we found that both RelB and cRel are persistently activated, suggesting BAFF-signaling coordinates both pathways to ensure robust B cell development. Indeed, we report now that combined loss of these two family NFκB members leads to impaired BAFF-mediated survival and development in vitro. While single deletion of RelB and cRel was dispensable for normal B cell development, double knockout mice displayed an early B cell developmental blockade and decreased mature B cells. Despite disorganized splenic architecture in Relb-/-cRel-/- mice, generation of mixed-mouse chimeras established the developmental phenotype to be B cell intrinsic. Together, our results indicate that BAFF signals coordinate both RelB and cRel activities to ensure survival during peripheral B cell maturation.

  • Submitted October 20, 2014.
  • Accepted December 29, 2015.