Autoimmune Disease in NZB/Bl Mice

Abstract

Abstract Malignant lymphoma was found in 4 of 20 NZB/Bl mice (of the 61st generation) selected for laboratory examinations and autopsy at 9 to 11 months of age. The malignant lymphomas were of two histologic types, reticulum cell sarcoma and pleomorphic malignant lymphoma, the latter term being used to designate malignant neoplasms arising in lymphatic tissue, composed of mesenchymal cells of diverse appearance—mainly plasma cells of blast, immature, mature and Russell-body types but also large primitive (stem) cells, reticulum cells, and lymphocytes of large and small size—and frequently associated with gammopathies. One of the reticulum cell sarcomas was transplantable to, and produced lethal disseminated growth in, other NZB/Bl mice. In each example of malignant lymphoma, warm hemagglutinins (to papain-treated mouse red cells) were demonstrable in serum. Autoimmune hemolytic disease and chronic membranous glomerulonephritis, both of common occurrence in NZB/Bl mice of comparable age, were also present. In one instance of pleomorphic malignant lymphoma, hypergammaglobulinemia of unusual quantity and quality drew attention to the possibility of lymphomatous disease. Some evidence was brought forth indicating that in the majority of instances the autoimmune diseases preceded the malignant lymphomas. While the coexistence of autoimmunity and lymphoid neoplasia conceivably reflects nothing more than chance occurrence, other interpretations were considered: the proliferative advantage engendered in immunologically competent cells in autoimmune disease may be a step in the direction of lymphoid neoplasia; or, in some instances autoantibodies may be produced by, or in response to, the neoplastic lymphoid cells.