NEGATIVE REGULATION OF APOPTOTIC DEATH IN IMMATURE B-CELLS BY CD45

Cross-linking of membrane IgM receptor on B cells induces tyrosine phosphorylation within 1 min. This biochemical alteration triggers a cascade of signaling events which ultimately leads to activation in mature B cells but growth arrest and cell death by apoptosis in immature B cells. To study the mechanisms underlying the bifurcation of signals, we chose to examine the role of receptor-type protein tyrosine phosphatase (PTP) CD45 using CD45(-) clones isolated from an immature B cell line WEHI-231. Here we report that in CD45(-) clones, tyrosine phosphorylation was constitutively induced but not enhanced by anti-Igm stimulation end anti-IgM-induced Ca2+ flux was slightly delayed but evidently prolonged. Further, the degree of growth arrest and DNA fragmentation induced by anti-IgM antibody was more evident in CD45(-) clones than the parental cells. These results indicate that initial alterations in signaling are effectively transduced into effector signals and that IgM receptor-mediated growth arrest and apoptosis in immature a cells are negatively regulated by CD45.