TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor.
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.
Gardam
Sandra
S
Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst NSW 2010, Australia.
Sierro
Frederic
F
Basten
Antony
A
Mackay
Fabienne
F
Brink
Robert
R
D000818:Animals; D053265:B-Cell Activation Factor Receptor / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology*; D047992:TNF Receptor-Associated Factor 2 / Q000276:immunology* / Q000378:metabolism; D048008:TNF Receptor-Associated Factor 3 / Q000276:immunology* / Q000378:metabolism
D053265:B-Cell Activation Factor Receptor; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3