Ku in the cytoplasm associates with CD40 in human B cells and translocatesinto the nucleus following incubation with IL-4 and anti-CD40 mAb

CD40 plays a critical role in survival, growth, differentiation, and class switching of B lymphocytes. Although Ku is required for immunoglobulin clas s switching, how CD40 signal transduction is coupled to Ku is still unknown . Here, we show that CD40 directly interacts with Ku through the membrane-p roximal region of cytoplasmic CD40. Ku was confined to the cytoplasm in hum an primary B cells, and the engagement of CD40 on the B cells cultured in t he presence of IL-4 resulted in the dissociation of Ku from CD40, transloca tion of Ku into the nucleus, and increase in the activity of DNA-dependent protein kinase. These findings indicate that Ku is involved in the CD40 sig nal transduction pathway and may play an important role in the CD40-mediate d events.