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. 1993 Aug;93(2):253–258. doi: 10.1111/j.1365-2249.1993.tb07975.x

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.

P Terness 1, U Marx 1, G Sandilands 1, D Roelcke 1, M Welschof 1, G Opelz 1
PMCID: PMC1554850  PMID: 8394233

Abstract

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/10(6) cells). This effect was competitively inhibited by F(ab')2 gamma. 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 IgG1 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 Fc gamma-receptor (Fc gamma R)-mediated 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 Fc gamma R. 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.

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Selected References

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