CD40 plays a critical role in survival, growth, differentiation, and class switching of B lymphocytes. Although Ku is required for immunoglobulin class switching, how CD40 signal transduction is coupled to Ku is still unknown. Here, we show that CD40 directly interacts with Ku through the membrane-proximal region of cytoplasmic CD40. Ku was confined to the cytoplasm in human primary B cells, and the engagement of CD40 on the B cells cultured in the presence of IL-4 resulted in the dissociation of Ku from CD40, translocation 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 signal transduction pathway and may play an important role in the CD40-mediated events.
Bibliographical noteFunding Information:
We thank B. Seed and T. Watanabe for cDNA constructs; E. A. Clark, S. M. Fu, T. Kobata, and T. Mimori for antibodies; K. Moore for IL-4: and all the members of R. S. G.'s lab, where this work was initiated. This work was supported by grants from Kato Memorial Foundation (T. M.) and from the Ministry of Education, Science, Sports, and Culture of Japan (T. M., H. T., and J. Y.).
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Infectious Diseases