A CELL-SURFACE RECEPTOR DEFINED BY A MAB MEDIATES A UNIQUE TYPE OF CELL-DEATH SIMILAR TO ONCOSIS

Cell death is mediated by distinct pathways including apoptosis and on cosis in response to various death signals. To characterize molecules involved in cell death, a panel of mAbs was raised by immunizing mice with apoptotic cells. One of these antibodies, designated anti-Porimin (for pro-oncosis receptor inducing membrane injury), was found to dir ectly induce a unique type of cell death in Jurkat cells. Anti-Porimin defines a 110-kDa cell surface receptor on Jurkat cells. Functionally , anti-Porimin alone rapidly mediates pore formation on the plasma mem brane and induces cell death without participation of complement. Both the cellular expression and functional characteristics of the Porimin antigen indicate that it is distinct from the CD95 (Fas/Apo-1) and ot her cell receptors known to induce apoptosis. Anti-Porimin-mediated ce ll death was preceded by cell aggregation, formation of plasma membran e pores, and the appearance of membrane blebs. More important, these c ells show neither DNA fragmentation nor apoptotic bodies, but display lethal damage of the cell membrane. Cell death by anti-Porimin is dist inct from complement-dependent cytolysis or complement-independent apo ptosis but is similar to that described for oncosis, a form of cell de ath accompanied by the membrane damage followed by karyolysis. The ind uction of cell death by anti-Porimin may represent a unique cell surfa ce receptor-mediated pathway of cell death in the human lymphoid syste m.