Suppression of anti‐erythrocyte autoantibody‐producing B cells by a physiological IgG‐anti‐F(ab')2 antibody and escape from suppression by tumour transformation; a model relevant for the pathogenesis of autoimmune haemolytic anaemia
We showed previously that broadly reactive IgG anti‐immunoglobulin autoantibodies produced by rats during the immune response suppress the B cell response. We report here on the effect of a similar human antibody on self‐reactive human B cells. IgG anti‐F(ab')2 was added to cultures of anti‐erythrocyte autoantibody‐producing B cells derived from healthy donors. A dose‐dependent suppression of the antibody response was obtained (maximum at 1.3 ng IgG/106 cells). This effect was competitively inhibited by F(ab')2γ. Autoimmune haemolytic anaemia can be caused by chronic monoclonal B cell proliferation. To reproduce this condition in vitro we immortalized B cells with Epstein‐Barr virus (EBV) and raised a B cell population with anti‐erythrocyte autoantibody activity. These cells were electrically fused with CB‐F7 tumour cells and an IgGl cold‐reactive anti‐erythrocyte autoantibody‐producing B cell line was established. Surprisingly, the tumour cells were not suppressed by IgG anti‐F(ab')2. It is known that anti‐immunoglobulins selectively suppress antigen‐receptor (AgR)‐occupied B cells by a Fcγ‐receptor (FeyRemediated mechanism. To occupy their AgR, we preincubated the tumour cells with anti‐AgR antibody. In spite of this, their susceptibility to suppression was not restored. As shown by rabbit IgG‐sensitized ox erythrocyte (EA)‐rosetting, this refractoriness was not due to a loss of FcγR. Our experiments delineate a mechanism of peripheral B cell suppression to autoantigens, and show a way of escape from control relevant for the pathogenesis of autoimmune haemolytic anaemia.