Response of lymphoid organs to immunization with Fc fragments of IgG carrying epitopes specific to regulatory rheumatoid factor

Abstract

Previously, we identified a new factor of autoimmunity downregulation, called regulatory rheumatoid factor (regRF). The production of regRF was associated with the resistance of animals to the experimental autoimmune diseases or with the remission in animals that are sensitive to the autoimmune diseases. The action of regulatory rheumatoid factor is based on the killing of activated CD4 T lymphocytes expressing PD-1, which makes it possible to restrain the expansion of lymphocytes, including autoreactive ones. RegRF-specific epitopes (regRF epitopes) can be induced on IgG Fc fragments. Immunization of rats with homologous IgG Fc fragments bearing regRF epitopes suppresses symptoms, lymphocytic infiltration and target tissue damage in several experimental models of autoimmune diseases. An in vitro study of the mechanisms of regRF-producing lymphocytes activation by IgG Fc fragments carrying regRF epitopes showed that IgG Fc fragments carrying regRF epitopes are T cell-independent antigens type 2. The reactions of the immune system, in particular in lymphoid organs, to T cell-independent antigens type 2, especially having a protein nature, are poorly studied. The purpose of this work is to study the reactions of the spleen and lymph nodes of rats to immunization with IgG Fc fragments carrying regRF epitopes. Wistar rats were immunized subcutaneously with 500 μg of homologous IgG Fc fragments carrying regRF epitopes. Control animals received an injection of phosphate-buffered saline. Immunization with IgG Fc fragments carrying regRF epitopes caused a transient increase of regulatory rheumatoid factor blood level with a maximum on day 7 after immunization. It was found that immunization with IgG Fc fragments carrying regRF epitopes does not cause a reaction in the regional and distal lymph nodes of rats, but induces the development of secondary follicles in spleen that exist for at least 28 days. On day 49, the number of follicles with germinal centers in the spleen of rats immunized with IgG Fc fragments carrying regRF epitopes was lower than in control rats. Consequently, the reaction of splenic follicles in rats immunized with IgG Fc fragments carrying regRF epitopes is transient. No changes were detected in the periarteriolar lymphoid sheaths (splenic T cell zone) in rats immunized with IgG Fc fragments carrying regRF epitopes. Thus, IgG Fc fragments carrying regRF epitopes, being a T cell-independent antigens type 2, do not cause a reaction in the lymph nodes, but induce the development of germinal centers in the spleen that exist for several weeks.