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PMID: 11101508 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 19 ·No. 23 ·2000-12-01 ·Pages 6351-60

Grossmann M, O'Reilly LA, Gugasyan R, Strasser A, Adams JM, Gerondakis S

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.

MeSH Terms
Animals Apoptosis B-Lymphocytes/cytology,metabolism CD4-Positive T-Lymphocytes/metabolism CD8-Positive T-Lymphocytes/metabolism Cell Survival Cells, Cultured Enzyme-Linked Immunosorbent Assay Flow Cytometry Fluorescent Antibody Technique Hematopoietic Stem Cells Immunoglobulin D/metabolism Liver/embryology Lymphocyte Activation Mice Mice, Inbred C57BL Mutation NF-kappa B/genetics,metabolism Phenotype Proto-Oncogene Proteins c-bcl-2/genetics,metabolism Proto-Oncogene Proteins c-rel/genetics,metabolism Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes/metabolism Time Factors Transcription Factor RelA Transcription Factors/metabolism Transgenes Up-Regulation
Chemicals
Immunoglobulin D NF-kappa B Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-rel Transcription Factor RelA Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Grossmann M
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Victoria 3050, Australia.
O'Reilly L A
Gugasyan R
Strasser A
Adams J M
Gerondakis S
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.23.6351
Published
2000-12-01
Pages
6351-60
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305873
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.23.6351 PMC Full Text View journal details
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