SUMMARYIn order to gain insight into the mechanisms by which the infusion of IgG can improve some autoimmune diseases, we induced haemolytic anaemia 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 erythrocyte sequestration in the spleen and liver, whereas the IgG2a antibody 34-3C triggers erythrophagocytosis (Shibata et al., 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 myeloma patients. Prior absorption by mouse erythrocytes did not affect the efficacy of the injected IgG. Treatment with Fc fragments also reduced the anaemia. In vitro experiments confirmed that 34-3C, but not 31-9D, triggered erythrocyte phagocytosis by murine macrophages. This process was completely inhibited by addition of polyclonal or myeloma IgG or of human Fc fragments. These results indicate that, in this model of autoimmune pathology, the protective effect of IgG is mediated by its interaction with the macrophage Fc receptors.

The administration of rabies ribonucleocapsid (RNP) by oral as well as parenteral routes was found to prime specific T cells and elicit N-protein-specific antibodies. per os and intramuscular immunization led to the production of antibodies of the IgA and IgG isotypes, respectively. Mice primed orally with RNP produced significantly enhanced amounts of virus-neutraliing antibody, compared with nonimmune controls, upon subsequent parenteral booster immunization with inactivated rabies virus. Thus oral immunization with rabies RNP primed cells capable of mediating a secondary systemic response to rabies virus. The results of experiments in which peptide and protein antigens were administered either physically coupled to or mixed with RNP indicate that RNP has an inherent capacity to enhance immune responses.

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Several autoimmune diseases, mainly autoantibody-mediated, are attenuated by infusion of total IgG (IVIg). The efficacy varies widely from one patient to another. Using an experimental model of in vitro phagocytosis of autoanti-body-coated erythrocytes by mouse macrophages, we analysed the possible causes for such a variability. Our results indicated that the efficacy of the phagocytosis inhibition depends upon different factors, such as the isotype and the extent of polymerization of the immunoglobulin used for the treatment as well as the genetic background of the mice and the state of macroph-age activation that can be influenced by concomitant viral infection. The development of an in vitro assay for the phagocytic activity of macrophages might improve the selection of patients susceptible to benefit from IVIg treatment.