Mice lacking the c-rel proto-oncogene exhibit defects in lymphocyte proliferation, humoral immunity, and interleukin-2 expression.
The c-rel proto-oncogene, which is expressed predominantly in hemopoietic cells encodes a subunit of the NF-kappa B-like family of transcription factors. In mice with an inactivated c-rel gene, whereas development of cells from all hemopoietic lineages appeared normal, humoral immunity was impaired and mature B and T cells were found to be unresponsive to most mitogenic stimuli. Phorbol ester and calcium ionophore costimulation, in contrast to certain membrane receptor-mediated signals, overcame the T cell-proliferative defect, demonstrating that T cell proliferation occurs by Rel-dependent and -independent mechanisms. The ability of exogenous interleukin-2 to restore T Cell, but not B cell, proliferation indicates that Rel regulates the expression of different genes in B and T cells that are crucial for cell division and immune function.
Köntgen
F
F
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Grumont
R J
RJ
Strasser
A
A
Metcalf
D
D
Li
R
R
Tarlinton
D
D
Gerondakis
S
S
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D001853:Bone Marrow / Q000254:growth & development / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006410:Hematopoiesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D020569:Proto-Oncogene Proteins c-rel; D011519:Proto-Oncogenes; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics
D007376:Interleukin-2; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors