INDUCTION OF ANTI-DNA ANTIBODIES BY IMMUNIZATION WITH ACTIVATED LYMPHOCYTES AND ACTIVE CHROMATIN

Objective To investigate the primary autoantigens which contribute to the production of anti-DNA antibodies. These antibodies are serologica l hallmark and pathogenic factor of systemic lupus erythematosus (SLE) . Methods Nonautoimmune predisposed BALB/c mice were immunized with co ncanavalin A (Con A) activated, lipopolysaccharide (LPS) activated and nonactivated syngeneic spleen cells, Nuclei and chromatin from activa ted/nonactivated lymphocytes were isolated and syngeneic mice were imm unized. Sera were taken after the third immunization. IgG anti-dsDNA a ntibody was determined by ELISA (calf thymus DNA treated with S1 nucle ase was used as the coated antigen). The glomerular IgG deposition was observed by immunofluorescence one month after the third immunization . Results Con A activated T cells and LPS activated B cells induced an ti-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 ant i-ds DNA antibody, but not resting chromatin isolated from nonactivate d Animals lymphocytes. Conclusions Activated lymphocytes and their act ive chromatin could be the autoimmunogen(s) driving the anti-dsDNA ant ibodies. The change of chromatin's antigenicity by environmental facto rs and genetic background may be the common pathway to SLE pathogenesi s.