PROLIFERATIVE ACTIVITY OF THE LYMPHATIC TISSUES OF RATS AS STUDIED WITH TRITIUM-LABELED THYMIDINE

Abstract

Cytokinetic data are presented, employing quantitation of H3DNA in the lymphatic tissues of normal rats serially sacrificed after H3Tdr administration. A marked difference in the patterns of initial labeling and label loss was observed between the thymus and peripheral lymphatic tissue. The data are compatible with other indications of rapid cell renewal in the thymus. There is suppression of initial uptake of H3Tdr into the DNA of each large lymphocytic progenitor cell in the thymus, apparently because of a feedback of thymidine containing material from small lymphocytes in the thymus. Depletion of the thymus of small cells, as by operative stress or whole body x-ray, leads to a marked increase in the uptake of H3Tdr into the DNA of large thymocytes. This finding, which is in agreement with the previous findings of Sugino et al. (33, 34) suggesting transfer of thymine nucleotides from small thymus lymphocytes to precursor cells, may or may not be related to the apparent transfer of DNA label between thymic cells. The evidence for the latter consists of the curvilinear dilution of the DNA label in the thymus proliferating cell population and the relationship between the rate of DNA label dilution in large cells and the H3DNA in the small cells in the thymus. After the DNA label in progenitor cells in the thymus and lymph nodes has entered the small cell population, the subsequent dilution of grains in these dividing cells follows the same slope as the loss of radioactivity from the entire lymph node. There is a long retention of some H3DNA label in the dividing lymph node cell population. This suggests that the loss of radioactivity from the dividing cells and from the small cell population as a whole occurs equally. This pattern prevails regardless of whether the percentage of large and small cells is altered experimentally. These findings can be explained by an interchange of the DNA nuclear label between small lymphocytes and large lymphocytes. This could occur by some process such as phagocytosis or pinocytosis, or by transformation of the small lymphocyte into a large, dividing cell. The data fit best with the latter possibility. All or any of these mechanisms would lead to an equilibration of the DNA label between large and small cells. This finding prevents the assignment of a finite life span to lymphocytes on the basis of DNA labeling kinetics. Nevertheless, there appear to be at least two different types of lymphocytes. One, the "thymus-type" lymphocyte, is found in the thymus cortex, bone marrow and germinal centers of lymphoid follicles. The other type, found abundantly in the widespread peripheral lymphatic tissue, shows a very prolonged retention of DNA label and is believed to be the recirculating, "immunologically committed" cells described by others. These cells do not appear to enter the thymus cortex.