Lymphocytes. 3. Distribution. Distribution of lymphocytes in health.

Abstract

Twenty years ago J. L. Gowans (1959) published rigorous evidence that lymphocytes circulate from blood to tissue to lymph in the rat. This suggested a definitive solution to a problem that had been clearly posed in 1885 by Walther Flemming, the discoverer of germinal centres. When he considered previous observations that the traffic of lymphocytes leaving a lymph node via the efferent lymphatic was much greater (by a factor of 10-20) than the traffic reaching the node via the afferent lymphatics it was clear to Flemming that the vigorous mitotic activity of lymphocytes within lymph nodes, both in germinal centres and elsewhere, was one factor that could account for the discrepancy between cell influx and cell efflux. More remarkably he perceived that the only alternative explanation was that lymphocytes leave the bloodstream within lymph nodes and recirculate back to the blood via efferent lymph. More than 70 years later it was shown, by exploiting tritiated thymidine, that lymphocytes recently produced by cell division within a resting lymph node could make only a minor contribution to the excess numbers leaving in the efferent lymph (Gowans, 1959; Hall and Morris, 1965a). The blood vessels from which lymphocytes entered the node in such large numbers were pinpointed by Gowans and Knight (1964) as specialised postcapillary venules in the thymus-dependent area of lymph nodes. In the 1920s histologists had been impressed by the plump endothelium of small veins in this situation. Zimmermann (1923) had tentatively suggested that the lymphocytes seen within the endothelial wall of these venules were migrating from the node into the blood. This view still has support based on the shape of lymphocyles as observed on histological sections. The direction in which the cells were moving before fixation has been inferred from their orientation in the vessel wall (for example, Norberg and Rydgren, 1978). The validity of this approach is questionable not just because of much other evidence in favour of the net migration of lymphocytes from the blood into the node (for example, Sedgley and Ford, 1976) but also because of contradictory results obtained by 63 other workers applying the same method (Anderson and Anderson, 1976). During the 1960s the astonishing diversity of the morphologically uniform small lymphocyte was gradually revealed. The diversity includes not only T and B populations but also several distinct maturational stages of each cell line. It also involves the production of clones or subsets of lymphocytes specific for each of the myriad antigens to which the body can respond. Not surprisingly, the migration of lymphocytes now seems much more complicated than could be conceived in 1959. Not only does each population show an individual migratory pattern but the migration of some lymphocytes from the blood into different organs is apparently due to distinguishable mechanisms.