PASSIVE TRANSFER OF AUTOIMMUNE DISEASE WITH ISOLOGOUS IgG1 AND IgG2 ANTIBODIES TO THE TUBULAR BASEMENT MEMBRANE IN STRAIN XIII GUINEA PIGS Loss of Self-Tolerance Induced by Autoantibodies* BY CLIVE L. HALLS

Guinea pigs sensitized with heterologous renal cortical tubular basement membrane (TBM) 1 preparations develop a characteristic form of autoimmune tubulointerstitial nephritis (anti-TBM disease) (1). Widespread cortical tubular damage occurs, together with an extensive interstitial infiltrate that includes lymphocytes, plasma cells, macrophages, and multinucleated giant cells (1-5). The disease is believed to be mediated by anti-TBM autoantibodies for several reasons: linear deposits of immunoglobulin are present along the TBM (1, 3); antibodies reactive with normal TBM can be demonstrated in the serum and in eluates from diseased kidneys (1, 4, 6, 7), and the disease can be transferred with serum containing anti-TBM antibodies (4-9). It has not been shown which immunoglobulin type mediates the disease, although IgG has been detected along the TBM (2-9). In the guinea pig there are two well characterized isotypes (subclasses) of IgG (IgG1 and IgG2) with distinctive biologic properties (10). IgG1 binds to basophils and mast cells (homocytotropic), mediates anaphylactic reactions (11, 12), and is not hemolytic in the usual complement assay, although it does fix complement by the alternative pathway (13-17). IgG2 initiates complement-mediated hemolysis by the classical pathway, binds to macrophages (cytophilic), and can mediate the hemorrhagic component of Arthus reactions (13-16, 18). However, there is not complete agreement on the roles of IgG1 and IgGs in these phenomena (14, 19) and little is known of the role of IgG1 and IgG2 in more complicated immunologic phenomena, such as autoimmune diseases (20). Preliminary data have suggested that IgG~ may transfer anti-TBM disease (9), but no other information is available.