SELECTIVE REGULATION OF LYN TYROSINE KINASE BY CD45 IN IMMATURE B-CELLS

It has been well established that protein-tyrosine phosphatase CD45 is critically involved in the regulation of initial tyrosine phosphoryla tion and effector functions of T and B cells, However, the signaling p athway governed by CD45 is not completely understood. In B cells, it h as not been unequivocally resolved as to which protein-tyrosine kinase s (PTKs) associated with B cell antigen receptor are regulated by CD45 in intact cells. As a first step toward the elucidation of CD45-initi ated signaling events, we have tried to identify physiological substra tes for CD45 by analyzing PTK activity in CD45-deficient clones recent ly generated from the immature B cell line WEHI-231. The results clear ly demonstrated that among PTKs examined (Lyn, Lck, and Syk), only Lyn kinase is dysregulated in the absence of CD45 such that without B cel l antigen receptor ligation, Lyn is hyperphosphorylated and activated in CD45-negative clones. Thus, Lyn seems to be a selective in vivo sub strate for CD45 in immature B cells.