CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification

The fate of B lymphocytes is dependent on intrinsic and B cell antigen rece ptor (BCR)-induced signals. These signals are interpreted and modified by r esponse regulators such as CD19 that govern mature B cell activation. The c urrent understanding of how CD19 governs B lymphocyte signaling is outlined in this review. Primarily, CD19 establishes a novel Src-family kinase ampl ification loop that regulates basal signal transduction thresholds in resti ng B cells. Moreover, CD19 amplifies Src-family kinase activation following BCR ligation. CD19 amplification of Lyn activity leads to processive phosp horylation of CD19 and downstream substrates including CD22. Phosphorylated CD19 recruits other effector molecules including Vav, Grb2, phosphoinositi de 3-kinase, phospholipase C gamma2, and c-Abl, which may contribute to CD1 9 regulation of B cell function. CD19/Lyn complex formation also regulates phosphorylation of CD22 and Fc gamma RIIB, which inhibit B cell signal tran sduction through the recruitment of the SHP1 and SHIP phosphatases. These o bservations provide insight into how CD19 governs the molecular ordering an d intensity of signals transduced in B cells, and how perturbations in CD19 expression or signaling function may contribute to autoimmunity.