c‐Rel is essential for B lymphocyte survival and cell cycle progression

JR Tumang, A Owyang, S Andjelic, Z Jin… - European journal of …, 1998 - Wiley Online Library
JR Tumang, A Owyang, S Andjelic, Z Jin, RR Hardy, ML Liou, HC Liou
European journal of immunology, 1998Wiley Online Library
Abstract c‐Rel is a lymphoid‐specific member of the NF‐κB/Rel family of transcriptional
factors. To investigate the role of c‐Rel in B lymphocyte function, we generated ac‐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 (PNAhi) phenotype. In vitro, c‐Rel (−/−) B cells proliferate poorly upon ligation of their …
Abstract
c‐Rel is a lymphoid‐specific member of the NF‐κB / 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 (PNAhi) 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 α 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, co‐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.
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