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, V(pre-B)/λ5/μ heavy chain/Ig-α/Ig-β), we examined pre-BCR- and BCR-mediated signaling events in human and mouse pre-B (Nalm-6, 697, NFS-5), immature a (IgM⁺ Daudi, WEHI-231) and mature a (IgM⁺IgD⁺ BALL1) cell lines. Anti-μ 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 a 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-α), immature a (PKC-α and -β) and mature a (PKC-β) cell lines. Anti-μ cross-linking induced PKC translocation from the cytosolic to the membrane compartment in immature and mature a cells, but did not have this effect in a pre-B cell line. Anti-p cross-linking induced tyrosine phosphorylation of the p85 and p110 subunits of phophatidylinositol 3-kinase (PI3-kinase) in both pre-B and B cell lines, but the pre-BCR induced PI3-kinase activation was Syk independent. Ligation of the pre-BCR complex thus triggers a characteristic signaling pattern in pre-B cells.