THE MODE OF ACTION OF TREATMENT BY IGG OF HEMOLYTIC-ANEMIA INDUCED BYAN ANTIERYTHROCYTE MONOCLONAL-ANTIBODY

In order to gain insight into the mechanisms by which the infusion of IgG can improve some autoimmune diseases, we induced haemolytic anaemi a in mice by the injection of anti-erythrocyte MoAbs derived from NZB mice by S. Izui (Geneva). The IgG1 antibody 31-9D induces anaemia by e rythrocyte sequestration in the spleen and liver, whereas the IgG2a an tibody 34-3C triggers erythrophagocytosis (Shibata er nl., Int Immunol 1990; 2:1133). Treatment of mice with pools of either human or mouse IgG clearly attenuated the anaemia induced by 34-3C, but not by 31-9D. Similar protection was obtained with human monoclonal IgGs from myelo ma patients. Prior absorption by mouse erythrocytes did not affect the efficacy of the injected IgG. Treatment with Fc fragments also reduce d the anaemia. In vitro experiments confirmed that 34-3C, but not 31-9 D, triggered erythrocyte phagocytosis by murine macrophages. This proc ess was completely inhibited by addition of polyclonal or myeloma Ige or of human Fc fragments. These results indicate that, in this model o f autoimmune pathology, the protective effect of IgG is mediated by it s interaction with the macrophage Fc receptors.