Normal Cellular Prion Protein is Preferentially Expressed on Subpopulations of Murine Hemopoietic Cells

We studied the expression of normal cellular prion protein (PrP(C)) in mouse lymphoid tissues with newly developed mAbs to PrP(C). Most of the mature T and B cells in the peripheral lymphoid organs do not express PrP(C). In contrast, most thymocytes are PrP(C+). In the bone marrow, erythroid cells and maturing granulocytes are PrP(C+). Approximately 50% of the cells in the region of small lymphocytes and progenitor cells also express PrP(C). Most of these PrP(C+) cells are CD43(+), but B220(-), surface IgM(-) (sIgM(-)), and IL-7R(-), a phenotype that belongs to cells not yet committed to the B cell lineage. Another small group of the PrP(C+) cell are B220(+), and some of these are also sIgM(+). The majority of the B220(+) cells, however, are PrP(C-). Therefore, PrP(C) is preferentially expressed in early bone marrow progenitor cells and subsets of maturing B cells. Supporting this interpretation is our observation that stimulation of bone marrow cells in vitro with PMA results in a decrease in the number of PrP(C+)B220(-) cells with a corresponding increase of sIgM(+)B220(high) mature B cells. This result suggests that the PrP(C+)B220(-) cells are potential progenitors. Furthermore, in the bone marrow of Rag-1(-/-) mice, there are an increased number of PrP(C+)B220(-) cells, and most of the developmentally arrested pro-B cells in these mice are PrP(C+). Collectively, these results suggest that PrP(C) is expressed preferentially in immature T cells in the thymus and early progenitor cells in the bone marrow, and the expression of PrP(C) is regulated during hemopoietic differentiation.