SIGNALING THROUGH CD40 RESCUES IGE BUT NOT IGG OR IGA SECRETION IN X-LINKED IMMUNODEFICIENCY WITH HYPER-IGM

The ligand for CD40 (CD40L) is a membrane protein on activated T cells that induces B cell proliferation and differentiation. Several mutati ons of the CD40L gene were reported responsible for defective class sw itching of B cells in an X-linked immunodeficiency with hyper IgM (X-H IM). We studied four affected males from three families and found thre e independent mutations including new mutations of CD40L gene. In ever y X-HIM patient tested, however, anti-CD40 plus IL-10 did not induce c lass switching from IgM to IgG or IgA, even in the presence of Staphyl ococcus aureus Cowan I strain (SAC). CD4+ T cell clones, expressing CD 40L, on their surface, also did not rescue IgG or IgA induction by X-H IM peripheral blood B cells in vitro. But signaling through CD40 induc ed both B cell proliferation and IgE secretion when IL-4 was added to the culture. Taken together, these results show that in vitro signalin g through CD40 rescues IgE but not IgG or IgA secretion by peripheral blood X-HIM B cells and suggest that in vivo CD40 and CD40L interactio n might be necessary for IgG and IgA differentiation in X-HIM.