The anti-apoptotic activities of Rel and RelA required during B-cell maturation involve the regulation of Bcl-2 expression
- Author(s)
- Grossmann, M; O'Reilly, LA; Gugasyan, R; Strasser, A; Adams, JM; Gerondakis, S;
- Details
- Publication Year 2000-12-01,Volume 19,Issue #23,Page 6351-6360
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- NF-KAPPA-B; TRANSGENIC MICE; TRANSCRIPTION FACTORS; T-CELLS; PROLIFERATIVE RESPONSES; EMBRYONIC LETHALITY; DEFICIENT MICE; DEATH; ABSENCE; LACKING
- Publisher's Version
- https://doi.org/10.1093/emboj/19.23.6351
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-12-01 12:00:00