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.
Piccinni
M P
MP
Department of Clinical Immunology and Allergology, University of Florence, Italy.
Macchia
D
D
Parronchi
P
P
Giudizi
M G
MG
Bani
D
D
Alterini
R
R
Grossi
A
A
Ricci
M
M
Maggi
E
E
Romagnani
S
S
D000943:Antigens, Differentiation / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001491:Basophils / Q000502:physiology; D015152:Blotting, Northern; D001854:Bone Marrow Cells; D002469:Cell Separation; D003432:Cross-Linking Reagents; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008407:Mast Cells / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D017452:Receptors, IgG
D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D003432:Cross-Linking Reagents; D012333:RNA, Messenger; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D015847:Interleukin-4