TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor.

Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst NSW 2010, Australia.
Immunity (Impact Factor: 19.75). 04/2008; 28(3):391-401. DOI: 10.1016/j.immuni.2008.01.009
Source: PubMed

ABSTRACT Tumor necrosis factor receptor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a cooperative and nonredundant manner to suppress nuclear factor-kappaB2 (NF-kappaB2) activation, gene expression, and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell-activating factor of the tumor necrosis factor family). However, deletion of either TRAF2 or TRAF3 from the T cell lineage did not promote T cell survival, despite causing extensive NF-kappaB2 activation. This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. Binding of BAFF to BAFF receptor reversed TRAF2-TRAF3-mediated suppression of B cell survival by triggering the depletion of TRAF3 protein. This process was TRAF2 dependent, revealing dual roles for TRAF2 in regulating B cell homeostasis.

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