Relationship of cell-cycle expression of Ia-like antigenic determinants on normal and leukemia human granulocyte-macrophage progenitor cells to regulation in vitro by acidic isoferritins

Abstract

An association has been established between human Ia-like (Ia) antigenic determinants, expression during DNA synthesis on granulocyte-macrophage colony forming cells (CFU-GM) and the regulatory action of acidic isoferritins in vitro. Treatment of human bone marrow cells with monoclonal-anti-Ia-like (Ia) plus complement inhibited colony and cluster formation by approximately 50% but did not affect pre-CFU-GM. Reduction of colonies and clusters was similar whether bone marrow cells were exposed to anti-Ia plus complement, high specific activity tritiated thymidine ((3)HTdr) or acidic isoferritins. No further decrease was apparent with (3)HTdr or acidic isoferritins after Ia-antigen(+) CFU-GM were removed, or with anti-Ia plus complement or acidic isoferritins after DNA synthetic phase (S-phase) CFU-GM were removed. Anti-Ia, without complement, did not reduce colony or cluster formation but did block the inhibitory action of acidic isoferritins. A relationship existed between Ia antigens and the activity of acidic isoferritins in the following ways: (a) The apparent loss of Ia-antigens from CFU-GM by 5 h in culture at 37 degrees C, but not at 27 degrees or 4 degrees C, was associated with nonresponsiveness to inhibition with acidic isoferritins, (b) Ia-antigen(-), noncycling pre-CFU-GM that were insensitive to acidic isoferritins could generate a population of Ia-antigen(+) cycling CFU-GM in vitro that were responsive to inhibition by acidic isoferritins, and (c) nondetectability of Ia-antigens on CFU-GM from patients with leukemia was associated with nonresponsiveness to inhibition by acidic isoferritins. These results implicate Ia-antigen(+) progenitor cells in the regulation of myelopoiesis in vitro and demonstrate that absence of Ia-antigens on patient CFU-GM is associated with imbalances in normal regulatory interactions in vitro. These findings may be of relevance to normal regulation and to the progression of leukemia.