ROLE OF JAK3 IN CD40-MEDIATED SIGNALING

CD40 is a member of the tumor necrosis factor receptor family and play s an important role in B-cell survival, growth, differentiation, and i sotype switching, Recently, CD40 has been shown to associate with JAK3 , a member of the family of Janus Kinases, which are nonreceptor prote in kinases involved in intracellular signaling mediated by cytokines a nd growth factors. To investigate the role of JAK3 in CD40-mediated si gnaling, we studied the effect of CD40 stimulation on B-cell prolifera tion, IgE isotype switching, and upregulation of surface expression of CD23, ICAM-1, CD80, and LT-alpha in JAK3-deficient patients. Our stud ies show that stimulation of B cells with monoclonal antibody to CD40 in the presence of interleukin-4 (IL-4) or IL-13 resulted in similar r esponses in JAK3-deficient patients and normal controls, This suggests that JAK3 is not essential for CD40-mediated B-cell proliferation, is otype switching, and upregulation of CD23, ICAM-1, CD80, and LT-alpha surface expression, (C) 1998 by The American Society of Hematology.