Normal cellular prior 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.