The anti-apoptotic activities of Rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression

Rel and RelA, individually dispensable for lymphopoiesis, serve unique functions in activated B and T cells. Here their combined roles in lymphocyte development were examined in chimeric mice repopulated with c‐ rel −/− rela −/− fetal liver hemopoietic stem cells. Mice engrafted with double‐mutant cells lacked mature IgM lo IgD hi B cells, and numbers of peripheral CD4 + and CD8 + T cells were markedly reduced. The absence of mature B cells was associated with impaired survival that coincided with reduced expression of bcl‐2 and A1 . bcl‐2 transgene expression not only prevented apoptosis and increased peripheral B‐cell numbers, but also induced further maturation to an IgM lo IgD hi phenotype. In contrast, the survival of double‐mutant T cells was normal and the bcl‐2 transgene could not rectify the peripheral T‐cell deficit. These findings indicate that Rel and RelA serve essential, albeit redundant, functions during the later antigen‐independent stages of B‐ and T‐cell maturation, with these transcription factors promoting the survival of peripheral B cells in part by upregulating Bcl‐2.