New insights into TRAF-mediated regulation of BAFF receptor signals (P1110) (original) (raw)

The Journal of Immunology

Abstract

BAFF receptor (BAFFR), a member of the TNFR superfamily, binds to the pro-survival cytokine BAFF to promote B cell development and survival, and deficiencies of either BAFFR or BAFF result in inhibition of B cell development. BAFF-R engagement recruits TRAFs 2, 3 and 6 and activates the non-canonical NF-κB2 pathway. Current models propose that TRAF3 mediates degradation of the NF-κB activating kinase NIK, concluding that BAFFR-mediated TRAF3 degradation is necessary and sufficient for NF-κB2 activation. However, our recent studies of a mutant BAFFR indicate that this model is inadequate to fully explain how BAFFR activates the NF-κB2 pathway. The A/WySnJ mouse harbors a spontaneous mutation of BAFFR in which 8 residues of the cytoplasmic tail are replaced by 22 amino acids from a viral genome. Engagement of this mutant BAFF-R fails to activate the NF-κB2 pathway, and A/WySnJ mice have a substantial B cell deficiency. However, the mutant BAFF-R shows no decrease in recruitment or rec...

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