Induction of Autoimmune Hemolytic Disease by Diffusible Substances from the Thymus of NZB/B1 Mice

‘-I-’ HE DEVELOPMENT BY BIELSCHOWSKY1 of the NZB/Bl strain of I mice has provided a unique animal model for the study of autoimmune disease. ’#{176} The regular spontaneous appearance of Coombs-positive hemolytic anemia and other serologic markers of autoimmunity, the development of a lupus-like renal disease,4’7’11’12 and the results of therapy with immunosuppressive agents4” and splenectomy#{176} are all consistent with the autoimmune concept of pathogenesis. Several studies have suggested a close relationship between the thymus and the autoimnmne disease of NZB/ BI mice. Burnet described an abnormal histologic pattern consisting of germinal centers with peripheral crescents of lymphocytes, increase in plasma cells, and lack of the expected atrophy with age.2’7 He drew attention to the similarity between these lesions and those of myasthenia gravis. DeVries and Hijmans noted a reduction in thymic epithelial cells.16 More significantly, transplantation of the NZB/B1 thymus to other mouse strains bed to the development of an autoimmune hemolytic disease in the recipients.5 We have confirmed these observations in an unpublished preliminarv experiment in which neonatally-thymectomized mice of other strains were transplanted subcutaneously with newborn NZB/ Bl thymus. Five of the 11 developed a positive Coombs’ test and other evidence of hemolytic disease. In this paper we present the results of studies suggesting that the NZB/B1 thymus releases a substance or agent capable of passing through the pores of a slillipore chamber and inducing hemolytic disease in the recipient host. The possible mechanisms involved in these observations and their interpretations are considered in the discussion.