Cross-linking of B cell antigen receptor-related structure of pre-B cell lines induces tyrosine phosphorylation of p85 and p110 subunits and activation of phosphatidylinositol 3-kinase.

To understand the function of B cell antigen receptor (BCR)-related complex on pre-B cells (pre-BCR, Vpre-B/lambda 5/mu heavy chain/Ig-alpha/Ig-beta), we examined pre-BCR- and BCR-mediated signaling events in human and mouse pre-B (Nalm-6, 697, NFS-5), immature B (IgM+ Daudi, WEHI-231) and mature B (IgM+ IgD+ BALL1) cell lines. Anti-mu cross-linking induced tyrosine phosphorylation of the cytoplasmic proteins in each cell type, but did not induce a detectable Ca2+ mobilization response in pre-B cells. While the pre-B cells expressed Syk protein at levels similar to those found in B cell lines, pre-BCR cross-linkage did not induce phosphorylation of Syk tyrosine residues. Different protein kinase C isozymes were expressed by pre-B (PKC-alpha), immature B (PKC-alpha and -beta) and mature B (PKC-beta) cell lines. Anti-mu cross-linking induced PKC translocation from the cytosolic to the membrane compartment in immature and mature B cells, but did not have this effect in a pre-B cell line. Anti-mu cross-linking induced tyrosine phosphorylation of the p85 and p110 subunits of phosphatidylinositol 3-kinase (P13-kinase) in both pre-B and B cell lines, but the pre-BCR induced P13-kinase activation was Syk independent. Ligation of the pre-BCR complex thus triggers a characteristic signaling pattern in pre-B cells.