CD40 ligation induces lymphotoxin alpha gene expression in human B cells.

CD40 plays an important role in T cell mediated B cell proliferation and isotype switching. The cytokines tumor necrosis factor (TNF)-alpha and lymphotoxin (LT)-alpha are expressed by B cells, and are known to play a role in B cell activation. We have studied TNF-alpha and LT-alpha expression in human tonsillar B cells following stimulation with anti-CD40 mAb. Anti-CD40 induced weak TNF-alpha mRNA expression but strong LT-alpha mRNA expression and had little effect on the constitutive expression of LT-beta mRNA in B cells. Induction of TNF-alpha mRNA was inhibited by actinomycin D suggesting that CD40 ligation results in transcriptional activation of the TNF-alpha and LT-alpha genes. Anti-CD40 caused minimal increase in the expression of TNF-alpha on the B cell membrane and no detectable secretion of TNF-alpha. Anti-CD40 as well as soluble CD40 ligand caused sustained induction of LT-alpha on the membrane of the B cells lasting up to 120 h but induced no detectable secretion of LT-alpha. IL-4, a cytokine known to synergize with anti-CD40 in inducing B cell proliferation and isotype switching, augmented the induction of LT-alpha mRNA and of mLT-alpha expression by anti-CD40. These results indicate that CD40 ligation vigorously induces expression of membrane LT-alpha in B cells and that membrane LT-alpha may play a role in CD40 mediated B cell activation.