Glucocorticoids upregulate CD40 ligand expression and induce CD40L-dependent immunoglobulin isotype switching

IL-4 and CD40 ligation are essential for IgE synthesis by B cells. We have shown previously that hydro-cortisone (HC) induces IgE synthesis in IL-1-st imulated human B cells. In this study we demonstrate that HC fails to induc e IgE synthesis in B cells from CD40 ligand-deficient (CD40L-deficient) pat ients. Disruption of CD40L-CD40 interactions by soluble CD40-Ig fusion prot ein or anti-CD4DL mAb, blocked the capacity of HC to induce IgE synthesis i n normal B cells. HC upregulated CD40L mRNA expression in PBMCs and surface expression of CD40L in PBMCs as vc ell as in purified populations of T and B cells. Upregulation of CD40L mRNA in PBMCs occurred 3 hours after stimul ation with HC and was inhibited by actinomycin D. Upregulation of CD40L mRN A and induction of IgE synthesis by HC were inhibited by die steroid hormon e receptor antagonist RU-486. These results indicate that ligand-mediated a ctivation of the glucocorticoid receptor upregulates CD40L expression in hu man lymphocytes.