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Tumang JR , Owyang A , Andjelic S , Jin Z , Hardy RR , Liou ML , Liou HC
c-Rel is essential for B lymphocyte survival and cell cycle progression
European Journal of Immunology. 1998 Dec;28(12) :4299-4312
Abstractc-Rel is a lymphoid-specific member of the NF-kappa B/Rel family of transcriptional factors. To investigate the role of c-Rel in B lymphocyte function, we generated a c-Rel(-/-) mouse via a gene targeting approach. Although early lymphocyte development is normal in c-Rel(-/-) mice, there are significantly fewer B cells displaying a memory (IgM/IgD(-)) phenotype. Upon immunization, c-Rel(-/-) mice generate fewer B cells with a germinal center (PNA(hi)) phenotype. In vitro, c- Rel(-/-) B cells proliferate poorly upon ligation of their surface IgM or CD40 receptors or when stimulated with either lipopolysaccharide (LPS) or T cell help. Early molecular events that precede proliferation, such as increases in RNA synthesis as well as IL-2 receptor cc chain expression, are greatly diminished in c-Rel(-/-) B cells. Furthermore, c-Rel(-/-) B cells are impaired in the ability to receive survival signals generated by anti-IgM or LPS. in contrast, CD40-mediated cell survival is normal in c-Rel(-/-) B cells, suggesting the involvement of a survival-signaling pathway that is independent of c-Rel. When c-Rel (-/-) B cells are co-stimulated with either anti-IgM and CD40 or LPS and CD40, they are rendered capable of progressing through the cell cycle. Finally, cc- culture experiments suggest that the defects observed in c- Rel(-/-) B cells are intrinsic to the cell and can not be rescued through either cell-cell contact or addition of soluble factors. Thus, c-Rel is requisite for differentiation to the germinal center and memory B cells in vivo and is required for the transduction of survival and cell cycle progression signals mediated by anti-IgM and LPS in vitro. Furthermore, while c-Rel is involved in CD40-induced proliferation, it is apparently dispensable for the survival signals transduced by CD40.
NotesTimes Cited: 24 English Article 148QC EUR J IMMUNOL