Accumulation of guanine-cytosine-enriched low M.W. DNA fragments in lymphocytes of patients with systemic lupus erythematosus.

The fate of the newly synthesized DNA in peripheral blood lymphocytes from patients with systemic lupus erythematosus was examined. After lymphocytes were stimulated with the mitogen phytohemagglutinin (PHA), DNA was pulse-labeled with radioactive thymidine and was analyzed by sucrose density gradient centrifugation. Two classes of DNA were identified; the main DNA fraction that migrated to the same position as that of control samples, and low m.w. DNA fragments. The low m.w. DNA fragments were further characterized: i) The amount of low m.w. fragments increased with increasing time of culture after PHA stimulation. ii) The guanine cytosine content was 47% of the total bases at 4 days after PHA stimulation. iii) The base composition was similar to that of DNA fragments isolated from DNA/anti-DNA antibody immune complexes. These results lead us to propose that guanine cytosine-enriched low m.w. DNA fragments accumulate in cells after nuclear DNA is degraded, and that these fragments may serve as a primary source of autoantigen for anti-DNA antibody production. In addition, they may interfere with normal cellular metabolism.