SIGNAL-TRANSDUCTION THROUGH MU-KAPPA B-CELL RECEPTORS EXPRESSED ON PRE-B CELLS IS DIFFERENT FROM THAT THROUGH B-CELL RECEPTORS ON MATURE B-CELLS

We introduced kappa light chain genes into pre-B cells to increase the surface mu HC expression, and established transfectants expressing ma ture type of B-cell receptors (BCR) on pre-B-cell surfaces. Since the cytoplasmic conformations of the reconstituted BCR and intrinsic pre-B -cell receptor (pre-BCR) are identical, they would be connected with t he identical signal transduction pathways in pre-B cells. By using the transfectants, we revealed that the reconstituted BCR on pre-B cells was functionally equivalent to BCR on mature B cells in terms of the i nduction of intracellular Ca++ mobilization. However, we found that th e signal-transduction pathways through BCR on pre-B cells were quantit atively different from those of BCR on mature B cells in two ways. Fir st, cross-linkage of the reconstituted BCR on pre-B cells induced pref erential tyrosine phosphorylation of p120 and p100, which was not obse rved when BCR on mature B cells was cross-linked. Second, BC-R in pre- B cells was physically associated with a larger amount of phosphatidyl inositol-3 kinase (PI-3K) than BCR in mature B cells in spite of the f act that both pre-B and B cells expressed a similar amount of PI-3K in cytoplasm. Signals through pre-BCR and BCR are known to cause distinc t biological effects in B-cell development. The biochemical features i n the downstream of reconstituted BCR on pre-B cells, which we reveale d in this study, will be of help in understanding the mechanism of fun ctional differences between pre-BCR and BCR.