CD40, BUT NOT LIPOPOLYSACCHARIDE AND ANTI-IGM STIMULATION OF PRIMARY B-LYMPHOCYTES, LEADS TO A PERSISTENT NUCLEAR ACCUMULATION OF RELB

In this study we analyzed the effect of CD40 stimulation on the activi ty and nuclear appearance of Rel/nuclear factor kappa B (NF-kappa B) f actors in primary murine B lymphocytes. We show that triggering of CD4 0 signaling pathway(s) by CD40 ligands expressed on L cells led to str ong activation of an NF-kappa B-controlled beta-globin reporter gene i n primary B lymphocytes from transgenic mice. Analyses of nuclear tran slocation of individual members of Rel proteins after CD40 induction o f primary B cells showed a strong and long-lasting accumulation of Rel B and, less pronounced, of c-Rel, LPS stimulation did not give rise to a persistent nuclear accumulation of RelB and c-Rel, whereas nuclear c-Rel, but not RelB, accumulated after B cell receptor stimulation, CD 40 induced not only nuclear translocation but also de novo synthesis o f RelB RNA and protein. S107 plasmacytoma cells, which express CD40 bu t are defective for the nuclear appearance of p51/p65-NF-kappa B, do n ot express RelB after CD40 stimulation, In S107 cells stably transfect ed with relB genes, stimulation of nuclear RelB translocation by CD40 was observed, These results indicate that stimulation of CD40 signalin g pathways exerts a long-lasting stimulatory effect on both the transc ription and nuclear translocation of RelB, Since LPS and anti-lgM were unable to activate RelB, CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes.