CD64 FC-GAMMA-RI IS A GRANULO-MONOCYTIC LINEAGE MARKER ON CD34(+) HEMATOPOIETIC PROGENITOR CELLS/

The aim of this study was to identify markers specific for granulo-mon ocytic commitment of progenitor cells. Large panels of antibodies were screened for selective staining of subsets of CD34(+) cells from feta l and adult bone marrow. Flow cytometric analysis showed that CD64/Fc gamma RI was undetectable on noncommitted progenitor cells (CD34(++), CD38(-/lo), HLA-DR(+)) and expressed on a subset of lineage-committed progenitors (CD34(+), CD38(+)) with higher mean orthogonal light scatt er than the remaining CD34(+) cells. The CD34(+), CD64(+) cells were C D19(-) and the majority were CD45RA(+), CD71(lo), suggesting that CD64 recognized granulomonocytic progenitor cells. Specificity of CD64 for the granulo-monocytic lineage was shown by demonstrating that colonie s arising from CD34(+), CD64(+) cells consisted of 98% +/- 2% colony-f orming unit-granulocyte-macrophage (CFU-GM) in semisolid medium contai ning stem cell factor (SCF), interleukin-3 (IL-3), IL-6, granulocyte-m acrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO) . In contrast, 63% +/- 15% of the colonies from the CD34(+), CD64(-) c ells were burst-forming unit-erythroid/colony-forming unit-erythroid ( BFU-E/CFU-E). Furthermore, four-color immunofluourescence and cell sor ting was used to analyze the progeny of cells cultured in liquid mediu m containing identical cytokines as used in the semisolid medium. This analysis showed that CD34(+), CD64(+) cells gave rise to 83% +/- 10% granulo-monocytic cells whereas progeny of the CD34(+), CD64(-) cells contained 81% +/- 11% erythroid cells. Neutrophils as well as basophil s and monocytes/macrophages were present in the cultures from CD34(+), CD64(+) cells, showing that this population contains progenitors of m ost types of granulo-monocytic cells. Two widely used myeloid markers, CD13 and CD33, were not myeloid-specific, because both were clearly p ositive on noncommitted progenitor cells. Of 40 antigens tested, CD15 was the only other marker fulfilling the criteria of a myeloid-specifi c marker. However, at concentrations of CD15 that did not induce aggre gation, CD15(+) cells constituted less than 50% of the CD34(+), CD64() cells. Furthermore, the CD64(+), CD15(-) cells showed more than 50% higher CD34 mean fluorescence intensity than the CD64(+), CD15(+) cell s, indicating that CD64 appears earlier than CD15 during differentiati on. Thus, among a large number of antigens screened, CD64 was the most useful for the identification and purification of granulo-monocytic p rogenitor cells. (C) 1995 by The American Society of Hematology.