Ontogenic development of macrophage subpopulations and Ia-positive dendritic cells in fetal and neonatal rat spleen.

Development, differentiation, and distribution of macrophage subpopulations and Ia+ dendritic cells in the fetal and neonatal rat spleen were investigated by means of double immunohistochemical staining and immunoelectron microscopy. To characterize these cell populations, a panel of anti-rat macrophage monoclonal antibodies (RM-1, ED2, ED3, TRPM-3, Ki-M2R) and an anti-rat Ia antibody (OX6) were used. In the fetal rat spleen, macrophages were first detected by RM-1 at fetal day 15. ED2+ and/or Ki-M2R+ macrophages appeared at fetal day 16. TRPM-3+ and/or ED3+ macrophages appeared a day later. During the fetal and neonatal development, ED2+ and TRPM-3+ macrophages differentiated independently, maturing into red pulp macrophages and marginal metallophilic and marginal zone macrophages respectively. Intimate topographical relations were observed between ED2+ macrophages and hematopoietic cells and between TRPM-3+ macrophages and marginal zone lymphocytes. Ia+ cells were first observed around arterioles at fetal day 15. In the fetal and neonatal period, the number of Ia+ cells gradually increased, their shape became dendritic, and they matured into interdigitating cells in the inner periarteriolar lymphatic sheath. In ontogeny, Ia+ dendritic cells were not stained with ED2 or TRPM-3. These results suggest that ED2+ macrophages, TRPM-3+ macrophages, and Ia+ dendritic cells are distinct cell lines that pursue independent developmental process in spleen ontogeny.