Fas-induced in vivo apoptosis in bone marrow: anti-Fas mAb-induced elimination and successive proliferation of Fas-expressing cells especially those of myeloid lineage.

A single administration of agonistic anti-Fas mAb RK8 into mice decreased the number of bone marrow cells especially Mac1+ and Gr1+ cells of myeloid lineage. These cells, which were shown to be Fas-positive in normal bone marrow, were directly eliminated in vivo by Fas-mediated apoptosis. After the elimination of Fas-positive bone marrow cells, bone marrow was reconstituted by successive increase of numbers of Gr1(low) and Mac1(low) myeloid precursor cells expressing high levels of Fas, which are minor constituents in normal bone marrow. The increased cells consisted at least two components, Gr1(dull) Mac1+ cKit+ cells and Gr1(intermediate) Mac1+ cKit- cells, both of which were shown to be sensitive to Fas-induced apoptosis in vivo. Thus, Fas is functional in normal bone marrow and Fas-induced apoptosis in bone marrow enhances marked proliferation of Fas-expressing myeloid precursor cells in vivo.