CD40 ligation induces lymphotoxin α gene expression in human B cells

Abstract

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