A systemic lupus erythematosus (SLE)‐like disease in mice induced by abnormal T‐B cell cooperation. Preferential formation of autoantibodies characteristic of SLE

Abstract

Abstract This is the first report describing the experimental induction of a full‐blown clinical syndrome strongly resembling systemic lupus erythematosus (SLE). The method used was the induction of a chronic graft‐ vs .‐host reaction (GVHR) employing genetically nonautoimmune strains of mice. Many of the F 1 mice undergoing a GVHR (GVH F 1 mice) revealed the following pathological alterations: splenomegaly, periarteritis, immunecomplex glomerulonephritis accompanied by elevated proteinuria and ascites, dysgammaglobulinemia, persistently increased production of IgG in the spleen, and formation of autoantibodies to thymocytes, erythrocytes, nuclear antigens, double‐stranded DNA, and antibodies deposited along the basement membrane of skin. In spite of the excessive T cell help, the GVH F 1 animals failed to produce spontaneous serum antibodies to dextran and the bacteriophage fd. They also had no increased numbers of spontaneous indirect plaque‐forming cells to sheep red blood cells and trinitrophenyl. These negative findings indicate that antigen has to be present during the GVHR to trigger antibody formation. This in turn suggests that the persistent presence of self‐antigens was essential for the formation of IgG autoantibodies in GVH F 1 mice. However, whereas autoantibodies typical of SLE were readily produced, none of the GVH F 1 mice had autoantibodies to thyroglobulin, or other autoantibodies not typical of SLE. Conceivably, not only the presence of self‐antigens, but also their antigenic configuration, may determine whether or not autoreactive B cells are successfully triggered during abnormal T‐B cell cooperation. Given the lack of carrier‐specific T helper cells in abnormal T‐B cell cooperation, protein self‐antigens, such as thyroglobulin, may be intrinsically less apt than the self‐antigens involved in SLE to bind to the corresponding autoreactive B cells. The self‐antigens involved in SLE, such as DNA and cell‐surface epitopes, are assumed to be capable of multipoint high‐avidity binding to and cross‐linking of the Ig receptors of these B cells, thus providing an effective signal 1.