Regulation of CD71⁺TER119⁺ erythroid progenitor cells by CD45

Red blood cells are generated daily to replenish dying cells and maintain erythrocyte homeostasis. Erythropoiesis is driven by erythropoietin and supported by specialized red pulp macrophages that facilitate enucleation. Here we show that the leukocyte-specific tyrosine phosphatase CD45 is downregulated in late erythroid development, yet it regulates the CD71⁺TER119⁺ progenitor pool, which includes the Pro E, Ery A, and Ery B populations. The CD71⁺TER119⁺ progenitors are a major splenic population in neonates required for extramedullary erythropoiesis, to meet the high demand for red blood cells during growth. This population decreases as the mice mature, but this was not the case in CD45-deficient mice, which maintained a high level of these progenitors in the spleen into adulthood. Despite these increased erythroid progenitors, CD45-deficient mice had normal numbers of mature red blood cells. This was attributed to the increased proliferation of the Pro E and Ery A populations and the increased apoptosis of the CD71⁺TER119⁺ population, as well as an increased turnover of circulating red blood cells. The expansion of the CD71⁺TER119⁺ population in the absence of CD45 was attributed to increased numbers of red pulp macrophages producing erythropoietin in the spleen. Thus, CD45 regulates extramedullary erythropoiesis in the spleen.