RECOMBINANT CD40 LIGAND STIMULATION OF MURINE B-CELL GROWTH AND DIFFERENTIATION - COOPERATIVE EFFECTS OF CYTOKINES

The ligand for the B cell surface antigen CD40 was recently cloned fro m a murine thymoma cDNA library and shown to be expressed on activated T cells. In this study, we investigate the biological effects of muri ne recombinant CD40 ligand. The recombinant CD40 ligand expressed on t he CV-1/EBNA monkey fibroblast cell line directly activated resting B cell to express elevated levels of cell surface class II major histoco mpatibility complex and CD23 molecules. CD40 ligand also stimulated B cell proliferation, reaching maximal levels on day 2 of culture and de clining thereafter. This effect was positively regulated by other cyto kines, most notably interleukin (IL)-4 and IL-5. By itself, CD40 ligan d had no effect upon immunoglobulin secretion by B cells. However, whe n B cells were treated with CD40 ligand plus cytokines, immunoglobulin secretion was stimulated in a cytokine-dependent and isotype-specific manner. IL-4 was a potent co-stimulator of IgE and IgG1 in the presen ce of CD40 ligand, and IL-5 acted synergistically with IL-4 in these r esponses as well as in IgM and IgG3 production. Taken together, the re sults indicate that CD40 ligand is a potent regulatory molecule for B cell growth and differentiation, and its activities are potentiated in a cytokine-specific manner.