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

M. Grossmann, L. A. O'Reilly, R. Gugasyan, A. Strasser, J. M. Adams, S. Gerondakis

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185 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6351-6360
Number of pages10
JournalThe EMBO Journal
Volume19
Issue number23
Publication statusPublished - 1 Dec 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • Lymphopoiesis
  • NF-κB
  • Transgenics

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