Modulation of thymic microenvironments during ontogeny and lymphomagenesis in mice was studied with two rat monoclonal antibodies (moAb) which recognized distinct subpopulations of thymic epithelial reticular cells (TER). In adult thymus, the TER subpopulation stained by moAb B6TS-1 was localized in the subcapsular zone, cortico-medullary junction, and medulla. In fetal thymus, it was initially distributed throughout the rudiment, but after day 16 of gestation, it was rapidly redistributed to the locations seen in adult thymus. From an early stage of thymic lymphomagenesis, the TER bearing mB6TS-1 (epitope defined by moAb B6TS-1) in the cortico-medullary junction, in particular those associating with small blood vessels, proliferated and formed a characteristic network throughout the thymus, in which numerous growing lymphoma cells were entrapped. On the other hand, moAb AKTS-1 stained another TER subpopulation that was localized in the cortex in both fetal and adult thymus. Unlike mB6TS-1+ TER, mAKTS-1+ TER became increasingly sparser during lymphomagenesis. Selective proliferation of the mB6TS-1+ TER subpopulation in the cortico-medullary junction was seen in spontaneous, radiation-induced, and chemical-induced mouse thymic lymphomas. The possible biological significance of such modulation of thymic microenvironments in the natural history of lymphomagenesis is discussed.

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