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Histoproliferative Effect of Rauscher Leukemia Virus on Lymphatic Tissue: Histological and Ultrastructural Studies of Germinal Centers and Their Relation to Leukemogenesis¹

Carcinogenesis Program, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830

The early histological and ultrastructural changes in lymphatic tissue were studied in adult BALB/c mice which had received i.p. injections of Rauscher virus preparation. The spleen, thymus, and mesenteric lymph node were studied at intervals between 6 hr and 20 days after injection. Special attention was given to the changes in germinal centers during the early phases of the Rauscher virus-induced leukemogenesis. Histologically, the singular distinct alteration in the Rauscher virus preparation-injected mice was a hyperplasia in the germinal centers, detected at 24 hr and continuing into what is described as "dissociative growth" of the center. Numerous C-type viruses were observed to be localized extracellularly in the plasma membrane infoldings of reticular cells which constitute the stroma of the centers. Between 4 and 7 days after Rauscher virus preparation injection, cells morphologically indistinguishable from those originally seen proliferating in the centers and eventually in the entire nodule were dispersed throughout the spleen red pulp. A most important aspect of this study was the identification in the spleen of immunoblasts participating in the replication of C-type particles. Budding of C-type particles from parenchymal immunoblasts of the germinal centers occurred as early as 24 hr after injection. By 7 days, the virus-replicating immunoblasts were detected in the spleen red pulp in close association with hematopoietic cells. It was suggested that the immunoblasts may, as a result of the sequential aspects of the events, provide a source of C-type virus to proliferating cells of the spleen red pulp, such as megakaryocytes and erythrocytic precursor cells. Viropexis among these cells in the red pulp was also observed at the latter intervals of this study. In general, these findings correlate with the antigen-localizing capacity of the stromal reticulum of the germinal centers, as well as overall immune suppression.

¹ Research sponsored jointly by the National Cancer Institute and the United States Atomic Energy Commission under contract with the Union Carbide Corporation.

Received 10/30/69. Accepted 2/12/70.