CD45 LIGATION INDUCES PROGRAMMED CELL-DEATH IN T-LYMPHOCYTE AND B-LYMPHOCYTE

Studies have shown an essential role for the CD45 protein tyrosine pho sphatase in regulating Ag receptor-derived signals in lymphocytes. Co- ligating CD45 with the Ag receptor, however, can also inhibit receptor signaling, as manifest in T cells by the lack of IL-2 production and proliferation. We report that CD45 ligation alone induces apoptosis in normal T cells, and that death was greatly potentiated by cross-linki ng CD3. Normal B cells and T and B cell lines were also induced to die with insoluble CD45 mAb. CD45-induced cell death was blocked by inhib itors of protein tyrosine kinases and protein tyrosine phosphatases, b ut not by inhibitors of RNA or protein synthesis or by cyclosporin A. Morphologically, CD45-mediated apoptosis resembled death induced via C D95 (Fas), as evidenced by nuclear condensation and membrane blebbing, but did not cause DNA fragmentation into oligonucleosomes. Co-ligatin g CD45 and CD95 either enhanced or inhibited CD45-induced cell death, depending on the degree of CD45 and CD95 cross-linking. Finally, CD45 cross-linking induced its rapid association with the detergent-insolub le cell fraction, suggesting that it becomes linked to the cytoskeleto n during CD45-induced apoptosis. These data show a novel role for CD45 in regulating lymphocyte death as well as proliferation.