Changes in cell surface antigen expression during murine bone marrow cell regeneration in vivo and proliferation in vitro.

Modulations in surface antigen expression during marrow regeneration in vivo, and proliferation in vitro in response to haemopoietic growth factors, were studied using a panel of monoclonal antibodies recognizing antigenic determinants expressed by primitive multipotential progenitor cells (Thy-1, Qa-m7), or lineage antigens restricted to committed progenitors and differentiated cells of the neutrophil/macrophage (7/4) and B lymphocyte (B220) lineages. These two categories of antigen exhibited differing responses to marrow perturbation and proliferation. Following administration of a cytotoxic dose of 5-fluorouracil, or lethal irradiation and transplantation of normal donor marrow, the levels of Thy-1 and Qa-m7 antigen expression rapidly increase, reaching a peak at the onset of regeneration: the nadir of marrow cellularity. Expression of these antigens returns to normal as regeneration proceeds and marrow is reconstituted. 7/4 and B220 antigen expression reflect the presence or absence of maturing cells bearing these markers: antigen expression declining following perturbation, and re-emerging during the course of regeneration. In vitro, when marrow cells taken from mice 8 days following treatment with 5-FU are grown in liquid culture in the presence of colony-stimulating factor-1 plus bladder cell carcinoma cell line 5637 conditioned medium, marrow cells are stimulated to proliferate and differentiate along the neutrophil/macrophage lineage. 7/4 antigen expression increases throughout the culture period, and B220 antigen is undetectable after the fifth day of culture. Thy-1 antigen expression also rises and remains elevated, and Qa-m7 antigen expression remains stable.