Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells

Abstract

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc?R I (MoAB 32.2), Fc?R II (MoAb IV-3), and Fc?R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc?R I is expressed exclusively on monocytes and macrophages, Fc?R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc?R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc?R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc?R I and Fc?R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc?R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc?R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc?R I, 58%; Fc?R II, 67%; and Fc?R III, 26% of patients. Despite the fact that Fc?R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American British [FAB] M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc?R I was highly correlated with FAB M4 and M5 morphology (P < .001). Fc?R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc?R I, but six cases were positive for Fc?R II and III (not the same patients). These studies demonstrate that Ig Fc?R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc?R.