Induction of the Ig chi 3 ' enhancer by distinct pathways can be inhibitedby cross-linking of the CD40 receptor

Upon treatment with lipopolysaccharide (LPS), primary B cells proliferate a nd differentiate into plasma cells with concomitant up-regulation of immuno globulin (Ig) gene expression. Here we examine the role of the Ig kappa 3' enhancer in this process using a kappa 3'-enhancer-driven P-globin reporter gene in transgenic mice. We find that LPS treatment up-regulates kappa 3' enhancer activity as a function of differentiation rather than proliferatio n, since proliferation only (induced by cross-linking of CD40) is insuffici ent to activate the element, whilst differentiation with only limited proli feration (LPS + transforming growth factor-beta) does allow activation to o ccur. The Ig kappa 3' enhancer is also induced by cross-linking of surface Ig and this signal can synergize with LPS activation, suggesting that disti nct activation pathways are used. Nevertheless, both of these pathways can be inhibited by co-cross-linking of CD40. Thus Ig enhancers in the heavy an d light chain loci are differentially regulated in response to CD40.