Evidence of extensive lymphocyte death in sheep Peyer's patches. II. The number and fate of newly-formed lymphocytes that emigrate from Peyer's patches.

The emigration of newly produced lymphocytes from Peyer's patches (PP) of lambs was studied. Mesenteric lymph nodes (MLN) were excised from most animals a few weeks after birth, and then at 8 to 10 wk of age, the dividing cells in 3 to 4 m of the small intestine were labeled in situ with [3H]thymidine. An extracorporeal perfusion system was used to restrict the 15-min period of labeling to the perfused lengths of intestine, which included either the large continuous ileal PP or a number of smaller jejunal PP. One or 3 days later, the number of labeled cells in the perfused tissue and in other lymphoid organs was studied by autoradiography. In the perfused tissues, labeled lymphocytes accounted for 63.7% of ileal PP cells by 1 day and for 86.7% by 3 days compared with only 9.6% of lymphocytes in the perfused MLN. Labeled lymphoid cells in the perfused PP were nearly all in the follicles. Labeled lymphocytes that must have been produced in the segments of ileum or jejunum at the time of the perfusion, subsequently emigrated via the lymphatics, and were identified in the spleen, MLN, other lymph nodes, blood, jejunal PP, and at a lower frequency in the thymus, nonperfused ileal PP, and bone marrow. In lymph nodes, spleen, and nonperfused PP, more than 80% of the immigrant newly formed PP-derived cells were small- and medium-sized lymphocytes, and about 15% were large lymphocytes. The nature of the labeled cells in the lamina propria of the nonperfused small intestine was quite different in that approximately 50% were plasma cells as early as 24 hr after the cells were born in the perfused gut. It is proposed that terminal B cell differentiation was most likely initiated within the PP in response to the entry of antigen. It was estimated that at both 1 and 3 days after perfusion there were about 100 times more labeled cells in the perfused ileal PP than could be accounted for by emigration to other organs. It was concluded that these results provide additional support for the view that PP in lambs produce a tremendous number of lymphocytes, but relatively few leave their site of production; most apparently die in situ.