Cooperation of multiple sign in CD40-regulated gene expr in B lymphocytes

CD40/CD40L interaction is essential for multiple biological events fa? in T dependent humoral immune responses, including B cell surm; vival and proliferation, germinal center and memory B cell formaex tion, and antibody isotype switching and affinity maturation. By in( using high-density microarrays, we examined gene expression in Fa primary mouse B lymphocytes after multiple time points of CD40L C] stimulation. In addition to genes involved in cell survival and si growth, which are also induced by other mitogens such as lipoC] polysaccharide, CD40L specifically activated genes involved in as germinal center formation and T cell costimulatory molecules that of facilitate T dependent humoral immunity. Next, by examining the at roles of individual CD40-activated signal transduction pathways, th we dissected the overall CD40-mediated response into genes h independently regulated by the individual pathways or collectively by all pathways. We also found that gene down-regulation is a significant part of the overall response and that the p38 pathway ac plays an important role in this process, whereas the NF-KB pathway go is important for the up-regulation of primary response genes. Our SC] finding of overlapping independent control of gene expression di' modules by different pathways suggests, in principle, that distinct pa biological behaviors that depend on distinct gene expression de subsets can be manipulated by targeting specific signaling pathways. Pri