The c-abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19

c-Abl is a nonreceptor tyrosine kinase that we have recently linked to grow th factor receptor signaling, The c-Abl kinase is ubiquitously expressed an d localizes to the cytoplasm, plasma membrane, cytoskeleton, and nucleus. T hus, c-Abl may regulate signaling processes in multiple subcellular compart ments. Targeted deletion or mutation of c-Abl in mice results in a variety of phenotypes, including splenic and thymic atrophy and lymphopenia, Additi onally,lymphocytes isolated from specific compartments of c-Abl mutant mice have reduced responses to a variety of stimuli and an increased susceptibi lity to apoptosis following growth factor deprivation, Despite these observ ations, little is known regarding the signaling mechanisms responsible for these phenotypes. We report here that splenic B cells from c-Abl-deficient mice are hyporesponsive to the proliferative effects of B cell Ag receptor (BCR) stimulation. The c-Abl kinase activity and protein levels are elevate d in the cytosol following activation of the BCR in B cell lines, We show t hat c-Abl associates with and phosphorylates the BCR coreceptor CD19, and t hat c-Abl and CD19 colocalize in lipid membrane rafts. These data suggest a role for c-Abl in the regulation of B cell proliferation downstream of the BCR, possibly through interactions with CD19.