HUMAN BONE-MARROW NON-B, NON-T CELLS PRODUCE INTERLEUKIN-4 IN RESPONSE TO CROSS-LINKAGE OF FC-EPSILON AND FC-GAMMA RECEPTORS

Human bone marrow (BM) cells lacking T- and B-cell markers expressed RNA encoding interleukin (IL) 4 and secreted detectable amounts of IL-4 in supernatants in response to Fc-epsilon or Fc-gamma-receptor (Fc-epsilon-R or Fc-gamma-R) cross-linking. In some experiments, IL-5 RNA expression in response to Fc-epsilon-R cross-linkage could also be detected. In contrast, RNA transcripts for, and secretion of, IL-2, IL-6, and interferon-gamma were never observed. The presence of IL-3 in the cultures was essential for IL-4 production by non-B, non-T BM cells in response to Fc-gamma-R cross-linking and enhanced IL-4 RNA expression in response to Fc-epsilon-R cross-linking. Under the same experimental conditions, BM T and B lymphocytes, as well as peripheral blood T, B, and non-B, non-T cells, did not express IL-4 RNA. Prolonged incubation of non-B, non-T cells in IgE-free medium followed by extensive washing did not inhibit IL-4 production induced by anti-IgE antibodies, suggesting that the Fc-epsilon-R involved in the response has the characteristics of a high-affinity receptor. The Fc-epsilon-R+ cells were separated from the Fc-epsilon-R- cells by sorting non-B, non-T BM cell suspensions with fluorescein isothiocyanate-conjugated IgE and then assessed for both IL-4 RNA expression and alcian blue staining. Both IL-4-producing and alcian blue-positive cells segregated with the Fc-epsilon-R+ fraction. These data suggest that human BM cells, probably belonging to the mast cell and/or basophil lineage, are capable of producing IL-4 in response to Fc-epsilon-R or Fc-gamma-R cross-linkage.