Mechanisms underlying cytotoxicity of anti-DNA antibodies

We studied mechanisms underlying cytotoxicity of catalytic anti-DNA autoantibodies or DNA abzymes isolated from the blood of patients with systemic lupus erythematosus and autoimmune mice. Experiments were performed on L929, HL-60, Raji, and K562 cells. Treatment with DNA abzymes caused internucleosomal DNA fragmentation in target cells typical of apoptosis. Direct immunofluorescence assay demonstrated that DNA abzymes can penetrate into the nucleus of target cells. The dependence of antibody-mediated cytotoxicity on the duration of incubation indicated that cell death is realized via at least 2 mechanisms: penetration of DNA abzymes into the cell nucleus followed by degradation of nuclear DNA or induction of apoptosis.