HLA-DR monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cells.
We studied the capacity of murine monoclonal antibodies with HLA-DR specificity to inhibit the proliferation in vitro of erythroid (BFU-E and CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells in normal bone marrow and the blood of patients with chronic granulocytic leukaemia (CGL). Two IgG2 antibodies (CA 2.06 and L243) inhibited the proliferation of normal BFU-E and CFU-GM at relatively high dilution; a third antibody, DA2, had no effect on either progenitor cell. A complement-fixing monoclonal antibody with T-cell activity (OKT3) produced only minor reduction in progenitor cel proliferation. Further studies with L243 showed that BFU-E and CFU-GM from the blood of patients with CGL were inhibited to the same degree as normal marrow progenitor cells. The inhibition of progenitor cell proliferation by a given antibody was always complement dependent and was therefore presumed to be due to a direct cytotoxic effect. The inhibitory effect of monoclonal antibodies is a valuable approach to the characterization of antigenic determinants on myeloid progenitor cells and the differential cytotoxicity of selected monoclonal antibodies might be exploitable for therapy.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002455:Cell Division; D003114:Colony-Forming Units Assay; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006684:HLA-DR Antigens; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D051379:Mice
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D003165:Complement System Proteins