SUPPRESSION OF ANTIERYTHROCYTE AUTOANTIBODY-PRODUCING B-CELLS BY A PHYSIOLOGICAL IGG-ANTI-F(AB')2 ANTIBODY AND ESCAPE FROM SUPPRESSION BY TUMOR TRANSFORMATION - A MODEL RELEVANT FOR THE PATHOGENESIS OF AUTOIMMUNE HEMOLYTIC-ANEMIA

We showed previously that broadly reactive IgG anti-immunoglobulin aut oantibodies produced by rats during the immune response suppress the B cell response. We report here on the effect of a similar human antibo dy on self-reactive human B cells. IgG anti-F(ab')2 was added to cultu res of anti-erythrocyte autoantibody-producing B cells derived from he althy donors. A dose-dependent suppression of the antibody response wa s obtained (maximum at 1.3 ng IgG/10(6) cells). This effect was compet itively inhibited by F(ab')2gamma. Autoimmune haemolytic anaemia can b e caused by chronic monoclonal B cell proliferation. To reproduce this condition in vitro we immortalized B cells with Epstein-Barr virus (E BV) and raised a B cell population with anti-erythrocyte autoantibody activity. These cells were electrically fused with CB-F7 tumour cells and an IgG1 cold-reactive anti-erythrocyte autoantibody-producing B ce ll line was established. Surprisingly, the tumour cells were not suppr essed by IgG anti-F(ab')2. It is known that anti-immunoglobulins selec tively suppress antigen-receptor (AgR)-occupied B cells by a Fcgamma-r eceptor (FcgammaR)-mediated mechanism. To occupy their AgR, we preincu bated the tumour cells with anti-AgR antibody. In spite of this, their susceptibility to suppression was not restored. As shown by rabbit Ig G-sensitized ox erythrocyte (EA)-rosetting, this refractoriness was no t due to a loss of FcgammaR. Our experiments delineate a mechanism of peripheral B cell suppression to autoantigens, and show a way of escap e from control relevant for the pathogenesis of autoimmune haemolytic anaemia.