Role of CD19 signal transduction in B cell biology.

Knockout studies have established an important role for the B lymphocyte surface protein CD19 in physiology. Previous studies by us and others have examined how CD19 might function at the biochemical level, with focus on the cytoplasmic tyrosines. We have mapped multiple different molecular associations with these tyrosines. However, the major question in CD19 signaling is, how do these tyrosines relate to what happens in vivo? To address this issue, we created mice expressing only mutant forms of CD19. Our initial studies have found that most CD19 function in vivo is dependent on two of these cytoplasmic tyrosines, Y482 and Y513. However, the signaling defects in cells expressing this mutation are subtle. They demonstrate that how CD19 signals depends on how it is ligated, and that CD19 signals by more than one mechanism. These observations in primary cells give insights into how CD19 functions at the molecular level and likely explain some of the differences in CD19 function that have been reported in vivo.