Evidence of extensive lymphocyte death in sheep Peyer's patches. I. A comparison of lymphocyte production and export.

Abstract

The metaphase arrest technique was used to determine the rate at which cells divide in the Peyer's patches (PP) and the thymus of 5 to 8 wk old lambs. The metaphase indices of these tissues were determined by analyzing cell suspensions of tissues taken before and 1, 2, 3, and 4 hr after metaphase arrest was initiated with i.v. vincristine. The metaphase indices increased in both tissues at a linear rate, which provided an estimate of the rate at which cells entered mitosis and of the lymphocyte birth rate. The ileal PP had the highest lymphocyte birth rate, 2.8% of the lymphocytes entered mitosis each hour; the rate was lower in jejunal PP (1.0%/hr) and thymus (0.5%/hr). With these values and estimates of the lymphocyte content in all PP (1.45 X 10(11)) and in the thymus (1.71 X 10(11)), it was calculated that the hourly lymphocyte production by PP in a lamb was 3.61 X 10(9) cells, which is four to five times greater than for the thymus (0.82 X 10(9)). Lymphocyte production in PP could then be compared with the number of lymphocytes that emigrated from the small intestine. Newly produced cells leave PP via the intestinal lymph, which could be collected from the entire small intestine after removal of the mesenteric lymph nodes. Cells entered the lymph at a rate of 0.8 X 10(9)/hr, but the output fell rapidly during chronic lymphatic drainage, a procedure known to deplete long-lived recirculating cells. It was concluded that most of the cells in intestinal lymph were recirculating cells, and newly formed lymphocytes produced in PP probably account for less than 25% of the total or 0.2 X 10(9)/hr. It seems unlikely that emigration could occur at a rate comparable with the rate of production in the PP. At most, only 5% of the PP cells seemed destined to leave their site of production, and it is proposed that most die within the PP follicles. The high mortality rate associated with the production of large numbers of B lymphocytes in lamb PP seems likely to have a significant impact on the nature of the contribution that these tissues make to the immune system.