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 func tions in activated B and T cells. Here their combined roles in lymphocyte d evelopment 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 CD4and CD8+ T cells were markedly reduced. The absence of mature B cells was a ssociated with impaired survival that coincided with reduced expression of bcl-2 and A1. bcl-2 transgene expression not only prevented apoptosis and i ncreased peripheral B-cell numbers, but also induced further maturation to an IgM(lo)IgD(hi) phenotype. In contrast, the survival of double-mutant T c ells was normal and the bcl-2 transgene could not rectify the peripheral T- cell: deficit. These findings indicate that Rel and RelA serve essential, a lbeit redundant, functions during the later antigen-independent stages of B - and T-cell maturation, with these transcription factors promoting the sur vival of peripheral B cells in part by upregulating Bcl-2.