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Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies directed against several nuclear components, such as DNA and histones. Apoptosis was induced in activated human lymphoblasts (n = 6) by UV-B irradiation for 30 sec followed by continuous culturing. An extranuclear accumulation of the nucleosomal histones H2A, H2B, H3, and H4 in cell lysates was observed very early in the process of apoptosis, even before phosphatidylserine externalization occurred on the outer membrane surface of apoptotically dying lymphoblasts. We hypothesize that a dysregulation of apoptosis during these early phases may contribute to the induction of autoimmunity against nuclear autoantigens as seen in SLE.