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Institute of Pathology,
Division of Neuropathology, and
Cancer Research Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106
We studied the expression of normal cellular prion protein (PrPC) in mouse lymphoid tissues with newly developed mAbs to PrPC. Most of the mature T and B cells in the peripheral lymphoid organs do not express PrPC. In contrast, most thymocytes are PrPC+. In the bone marrow, erythroid cells and maturing granulocytes are PrPC+. Approximately 50% of the cells in the region of small lymphocytes and progenitor cells also express PrPC. Most of these PrPC+ 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 PrPC+ cell are B220+, and some of these are also sIgM+. The majority of the B220+ cells, however, are PrPC-. Therefore, PrPC 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 PrPC+B220- cells with a corresponding increase of sIgM+B220high mature B cells. This result suggests that the PrPC+B220- cells are potential progenitors. Furthermore, in the bone marrow of Rag-1-/- mice, there are an increased number of PrPC+B220- cells, and most of the developmentally arrested pro-B cells in these mice are PrPC+. Collectively, these results suggest that PrPC is expressed preferentially in immature T cells in the thymus and early progenitor cells in the bone marrow, and the expression of PrPC is regulated during hemopoietic differentiation.
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