Production of autoantibodies to cellular antigens by human B cells transformed by Epstein-Barr virus.

Lymphocytes obtained from the blood of three patients who lacked clinical and serologic evidence of autoimmunity were inoculated with Epstein-Barr virus (EBV) and plated in microwell cultures at low cell densities. Large numbers of the resulting transformed cell lines produced IgM autoantibodies which reacted by ELISA with antigens in cultured human fibroblasts. Precursor frequencies of autoantibody-secreting transformed cells ranged from 27 to 630 per 10(6) cells. Autoantibodies from 20 ELISA-positive cell lines were studied by indirect immunofluorescence and found to react with a variety of highly conserved cellular antigens. Eleven cell lines were tested for the production of multiple isotypes; six of these cell lines produced both IgM and IgG autoantibodies. Findings point to the existence in normal human beings of a sizable population of B cells committed to synthesize a broad spectrum of autoantibodies and demonstrate that EBV transformation provides a potent tool for exploring the normal human B-cell repertoire.