Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation

Two different Fc receptors for IgG (Fc(γ)R) have been identified on human leukocytes: a high avidity receptor (Fc(γ)R(hi)) present on monocytes but not on neutrophils, and a low avidity receptor (Fc(γ)R(lo)) present on neutrophils but not on monocytes. Fc(γ)R(lo) can be inhibited and the receptor precipitated by monoclonal antibody 3G8. We have used this monoclonal antibody to study the course of FcγR(lo) appearance on bone marrow cells, leukocytes of patients with chronic myelogenous leukemia (CML), and HL-60 and U937 cells induced to differentiate with agents such as dimethyl sulfoxide (DMSO), retinoic acid, phorbol myristate acetate, and lymphokine. We report that Fc(γ)R(lo) is a late differentiation antigen, first expressed at the metamyelocyte stage. Since precursors to metamyelocytes bear Fc(γ)R, and the promyelocyte line HL-60 bears Fc(γ)R(hi), there must be a progressive loss of Fc(γ)R(hi) during myeloid differentiation and the reciprocal expression of Fc(γ)R(lo). Results of immunoprecipitation and polyacrylamide gel analysis of the proteins are consistent with these results. We have also studied the receptor for the C3bi complement component (CR3), which is blocked and immunoprecipitated by monoclonal antibody OKM10. During DMSO-driven differentiation of HL-60 cells, we find that CR3 is induced on all cells, whereas Fc(γ)R(lo) is induced on only 24% of cells, suggesting that CR3 appears earlier during differentiation than Fc(γ)R(lo) does.