Analysis of the genetic control of lymphocyte positioning.

Abstract

A possible role for the major histocompatibility complex (MHC) in the localization of lymphocytes in different lymphoid organs was investigated using inbred mouse strains. Lymphocytes labelled with the intracellular fluorochrome Hoechst 33342 (H33342) were transfused intravenously (IV) into unimmunized mice and the distribution of these labelled lymphocytes examined. In some combinations (e.g. C57BL/6----CBA) 2 h after injection allogeneic lymphocytes accumulated in the region between the marginal zones and outer aspects of the white pulp of the spleen. In contrast, in syngeneic controls (e.g. CBA----CBA) the lymphocytes migrated normally into the while pulp. Similar results were obtained in Peyer's patches. Mapping studies in the spleen indicated that the failure to migrate normally is predominantly controlled by the MHC complex, although some non-MHC genes may play a role. In the case of the MHC the most definitive combination was BALB/c-H-2dm2 (H-2L deletion mutant) lymphocytes transfused into BALB/c recipients, the mutant lymphocytes failing to migrate normally and, therefore, implicating the H-2L region in the phenomenon. No differences in the viability of labelled lymphocytes at 6 and 24 h after injection into either syngeneic or allogeneic recipients suggests that the inability of cells to passage through lymphoid organs may represent inappropriate receptors rather than elimination of the allogeneic lymphocytes by natural killer cells (NK) as previously proposed.