Erythrocyte replacement precedes leukocyte replacement during repopulation of W/Wv mice with limiting dilutions of +/+ donor marrow cells.

The severe macrocytic anemia of the stem-cell-deficient W/Wv mouse is alleviated by intravenous injection of normal marrow cells. Donor cells replace the host erythrocytes, but the fate of the more labile blood components, such as granulocytes and platelets, after transplantation into adult mice has not been established. In the present work, the rate of replacement of the various hemopoietic cells in W/Wv transplant recipients was examined by exploiting host-donor differences in cellular markers (hemoglobin and glucose-phosphate isomerase). Limiting dilutions of +/+ parental cells were injected into F1-hybrid W/Wv anemic mice. A dose of 10(5) donor cells was necessary for the implantation of sufficient multipotent stem cells to alleviate the anemia. Erythrocyte parameters were not significantly different from normal values, and donor cells replaced at least 90% of the host erythrocytes by 20 weeks after injection. At this time, only 10% of the nucleated leukocytes and none of the platelets were donor-derived. The percentage of donor lymphocytes, granulocytes, and platelets increased slowly thereafter but did not completely replace the host elements by 41 weeks. The maintenance of host leukocytes during rapid donor-erythrocyte replacement indicates cell-specific amplification of committed progenitors.