We generated spontaneous splenic B cell hybridomas and used microscopy to screen for clones reactive with apoptotic Jurkat cells. From hybridomas secreting IgG antibodies reactive with apoptotic cells, we selected one. The antibody, LHC7.15, bound to an antigen that is differentially distributed between the nucleus and the cytoplasm in live and apoptotic cells. In late apoptotic cells, the antigen coalesces into aggregates that bleb from the cell surface. Immunopurification of the antigen, followed by mass spectrometry, identified a protein of 60 kD whose parptial sequence matched heterogeneous nuclear ribonucleoprotein P2. This multi-functional protein bliinds DNA, RNA, and several known RNP autoantigens.