The combined absence of NF-kappa B1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells.
Transcription factors NF-kappaB1 and c-Rel, individually dispensable during embryogenesis, serve similar, yet distinct, roles in the function of mature hemopoietic cells. Redundancy among Rel/NF-kappaB family members prompted an examination of the combined roles of c-Rel and NF-kappaB1 by using mice that lack both proteins. Embryonic development and the maturation of hemopoietic progenitors were unaffected in nfkb1(-/-)c-rel(-/-) mice. Peripheral T cell populations developed normally, but follicular, marginal zone, and CD5(+) peritoneal B cell populations all were reduced. In culture, a failure of mitogen-stimulated nfkb1(-/-)c-rel(-/-) B cells to proliferate was caused by a cell cycle defect in early G(1) that prevented growth. In vivo, defects in humoral immunity and splenic architecture seen in nfkb1(-/-) and c-rel(-/-) mice were exacerbated in the double mutant mice. These findings demonstrate that in the B lineage overlapping roles for NF-kappaB1 and c-Rel appear to be restricted to regulating the activation and function of mature cells.
Pohl
Thomas
T
The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Gugasyan
Raffi
R
Grumont
Raelene J
RJ
Strasser
Andreas
A
Metcalf
Donald
D
Tarlinton
David
D
Sha
William
W
Baltimore
David
D
Gerondakis
Steve
S
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D006410:Hematopoiesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*
D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel