1568 Stem Cells for the Myeloid and Lymphoid Systems

The bone marrow of the adult mouse contains stem cells that continuously replenish the myeloid and lymphoid systems (1-4). The best characterized of these stem cells is that which differentiates into myeloid cells, i.e., erythrocytes, granulocytes, and megakaryocytes. This cell can easily be measured by its ability to form macroscopic colonies in the spleens of irradiated mice (5). Using radiation-induced chromosome aberrations, Wu et al. (6) showed conclusively that each spleen colony was a clone and that the stem cells, hemoglobin-synthesizing cells, and granulocytes in individual colonies were derived from a single precursor. Numerous indirect studies have shown a close relationship between these spleen colony-forming units (CFU-S) 1 and the lymphoid system (7-12), but no one has demonstrated directly that CFU-S are the precursors of functional lymphocytes. Because of the existing uncertainty regarding the precise relationships between the differentiation of myeloid cells and of B and T lymphocytes, we have attempted to devise an experimental system in which to analyze the early events in the differentiation of these cells. The work described below had two objectives: (a) To obtain direct evidence for the existence of a class of pluripotent stem cells that can be the progenitors of functional B and T lymphocytes, as well as myeloid cells, and (b) to look for the existence in adult bone marrow of stem cells restricted to differentiation along one pathway. That is, we looked for stem cells that give rise only to myeloid cells or only to lymphoid cells.