Decreased surface IgM receptor-mediated activation of phospholipase C gamma 2 in B-1 lymphocytes.

Intracellular signaling triggered by the antigen receptor of primary B-1 (CD5+ B) lymphocytes is insufficient to bring about cell cycle progression to S phase; this appears to result from a block in signal propagation prior to the activation of protein kinase C. The present studies were undertaken to evaluate specific elements in the proximal portion of the intracellular signaling cascade to determine the basis for aberrant signal transduction in B-1 cells. There was no evidence for an alteration in src kinase composition or for diminished receptor mediated tyrosine phosphorylation on the part of B-1 cells. Further, phospholipase C gamma 2 was inducibly tyrosine phosphorylated following surface Ig ligation. However, the receptor mediated increase in enzymatic activity of immunoprecipitated phospholipase C gamma 2 was markedly diminished in B-1 as compared with B-2 cells. These results indicate that phospholipase C gamma 2 largely fails to become activated following surface Ig receptor interaction in B-1 cells and suggest that this enzyme may be directly involved in controlling the propagation of progression signals.