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 a cell antigen receptor (BCR)-related co mplex on pre-B cells (pre-BCR, V-pre-B/lambda 5/mu heavy chain/lg-alph a/lg-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 i n each cell type, but did not induce a detectable Ca2+ mobilization re sponse 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 d id not induce phosphorylation of Syk tyrosine residues, Different prot ein 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 cros s-linking induced PKC translocation from the cytosolic to the membrane compartment in immature and mature a cells, but did not have this eff ect in a pre-B cell line, Anti-mu cross-linking induced tyrosine phosp horylation of the p85 and p110 subunits of phophatidylinositol 3-kinas e (Pl3-kinase) in both pre-B and a cell lines, but the pre-BCR induced Pl3-kinase activation was Syk independent, Ligation of the pre-BCR co mplex thus triggers a characteristic signaling pattern in pre-B cells.