Induction of anti-DNA antibodies by immunization with activated lymphocytes and active chromatin

To investigate the primary autoantigens which contribute to the production of anti-DNA antibodies. These antibodies are serological hallmark and pathogenic factor of systemic lupus erythematosus (SLE).

Nonautoimmune predisposed BALB/c mice were immunized with concanavalin A (Con A) activated, lipopolysaccharide (LPS) activated and nonactivated syngeneic spleen cells. Nuclei and chromatin from activated/nonactivated lymphocytes were isolated and syngeneic mice were immunized. Sera were taken after the third immunization. IgG anti-dsDNA antibody was determined by ELISA (calf thymus DNA treated with S1 nuclease was used as the coated antigen). The glomerular IgG deposition was observed by immunofluorescence one month after the third immunization.

Con A activated T cells and LPS activated B cells induced anti-double stranded (ds) DNA antibody in syngeneic nonautoimmune BALB/c mice and formed the glomerular IgG deposition. Further studies showed that active chromatin isolated from activated lymphocytes induced anti-ds DNA antibody, but not resting chromatin isolated from nonactivated lymphocytes.

Activated lymphocytes and their active chromatin could be the autoimmunogen(s) driving the anti-dsDNA antibodies. The change of chromatin's antigenicity by environmental factors and genetic background may be the common pathway to SLE pathogenesis.