Increased Qa-m7 antigen expression is characteristic of primitive hemopoietic progenitors in regenerating marrow.

Abstract

Developmentally early murine hemopoietic progenitor cells of high proliferative potential (HPP-CFC), which are detectable in clonal agar culture in the presence of the lineage-specific hemopoietic growth factor, colony-stimulating factor-1 (CSF-1) plus hemopoietin-1 (H-1), or interleukin 3 (IL 3), express relatively high levels of the Qa-m7 antigenic determinant. This determinant is progressively lost during differentiation, and the more committed progenitors which grow in the presence of CSF-1 alone are essentially devoid of Qa-m7. Significant increases in both the proportion of Qa-m7-positive myeloid cells and the level of Qa-m7 antigen expression have been observed in bone marrow cells regenerating after the administration of the cytotoxic agent 5-fluorouracil (5-FU). By exploiting this increase in Qa-m7 antigen expression during regeneration and the HPP-CFC-sparing properties of 5-FU, we have been able to enrich HPP-CFC from marrows 8 days post-5-FU treatment (FU8d) to purities of greater than 20%. Furthermore, discontinuous gradient centrifugation and fluorescence-activated cell sorting of FU8d bone marrow cells on the basis of their light-scattering properties and Qa-m7 expression has unmasked a further subset of HPP-CFC which strictly requires the combined stimulus of three hemopoietic growth factors (H-1, IL 3, and CSF-1) for clonal growth. These highly enriched subsets of HPP-CFC are either identical to or co-fractionate with transplantable multipotential hemopoietic progenitors capable of reconstituting the hemopoietic system of lethally irradiated mice. Up to one in three cells in these highly enriched fractions is an HPP-CFC, and up to one in two cells may be CFU-S assayed 13 days post-transplantation. In addition, these fractions contain progenitors capable of reconstituting the platelet, erythroid, and myeloid compartments of the marrow.