Rapid STAT phosphorylation via the B cell receptor - Modulatory role of CD19

Engagement of the B cell receptor (BCR) initiates multiple signaling cascad es which mediate different biological responses, depending on the stage of B cell differentiation, antigen binding affinity, and duration of stimulati on. Aggregation of co-receptors such as CD19 with the antigen receptor has been suggested to modulate the signals necessary for the development and fu nctioning of the humoral immune system. In this study, we demonstrate that engagement of the antigen receptor on peripheral blood B cells, but not nai ve splenic B lymphocytes, leads to rapid phosphorylation of signal transduc ers and activators of transcription 1 (STAT1) on Tyr-701 and Ser-727, Inter estingly, phosphorylation on tyrosine diminished with increased stimulation , whereas serine phosphorylation correlated directly with the level of BCR cross linking. In contrast, phosphorylation of STAT3 occurs exclusively on serine and is sensitive to inhibitors of the PI3-kinase and the ERK1/2 path ways. Finally, we show that co ligation of CD19 with the BCR results in inc reased tyrosine phosphorylation of STAT1 relative to BCR cross-linking alon e, establishing CD19 as a positive modulator of BCR-mediated STAT activatio n.