CD19-dependent activation of Akt kinase in B-lymphocytes

CD19 is rapidly phosphorylated upon B-cell antigen receptor (BCR) cross-lin king, leading to the recruitment of downstream signaling intermediates. A p rominent feature of CD19 signaling is the binding and activation of phospho inositide S-kinase (P13K), which accounts for the majority of PI3K activity induced by BCR ligation. Recent findings have implicated activation of the serine/threonine kinase Akt as imparting survival signals in a PI3K-depend ent fashion. Using CD19-deficient B-lymphhoma cells and mouse splenic B-cel ls, we show that CD19 is necessary for efficient activation of Akt followin g cross-linking of surface immunoglobulin or Ig beta, In the absence of CD1 9, Akt kinase activity is reduced and transient. In addition, coligation of CD19 with surface immunoglobulin leads to augmented Akt activity in a dose -dependent manner. Thus, CD19 is a key regulator of Akt activity in B-cells ; as such it may contribute to pre-BCR or BCR-mediated cell survival in viv o.