CELLULAR DIFFERENTIATION IN THE THYMUS

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Abstract
SUMMARY In Lewis rats, irradiated (900 r) and given syngeneic or (Lewis × BN) F1 bone marrow, cellular repopulation of the thymus, lymph nodes, and Peyer's patches was studied by conventional histological methods, by analysis of expressed cell suspensions with an electronic particle counter, and by an immunofluorescence technique for identifying histocompatibility and thymus-specific antigens. Cells of bone marrow origin (bearing the BN antigen) first appeared in the thymus at 4 days. In the subsequent 4-day period, the total number of thymus cells began to rise rapidly. At first, a high proportion were large or medium sized cells in which BN antigen could be detected; these made up almost one-half of the thymus cell suspensions in some animals at 6 days. By 8 days, small thymocytes, lacking either BN or Lewis antigen detectable by immunofluorescence, had largely replaced these larger cells. Both small and large cells possessed a thymus-specific antigen demonstrable by immunofluorescence. The 8-day pattern was comparable to that seen in normal rat thymus. Bone marrow-derived cells appeared in the lymph nodes at 6 days and in large numbers only several days later. In the Peyer's patches, they were first seen at 11 days. Cells taken from the repopulated thymus at 6 days and injected into partially irradiated recipients homed in the irradiated bone marrow in considerable numbers. Their ability to return to marrow fell off rapidly after 6 days. Their progeny in the marrow were all lymphocytic (i.e., not erythrocytic, myelocytic, etc.). It was concluded that bone marrow-derived cells which repopulate the thymus have the ability to return to the marrow although they are unipotential, i.e., committed to a lymphocytic differentiation. They lose this ability as their size shifts from large to small and as histocompatibility antigen in their cell membrane diminishes below detectable levels and is replaced by thymus-specific antigen.