title: C-fms protein expression by B-cells, with particular reference to the hairy cells of hairy-cell leukaemia.
abstract: Although the hairy cells (HCs) of hairy cell leukaemia (HCL) are now thought to be a form of activated B cell, they have long been known to possess certain monocytoid characteristics. Since the proto-oncogene c-fms is a feature of cells of the monocyte/macrophage lineage, we examined HCs for c-fms expression. We found that approximately 80% of peripheral blood HCs expressed the c-fms protein (8/8 cases). Expression of the 150 kD protein by HCs was shown using three different techniques, APAAP, immunofluorescence and immunoprecipitation, using two different antibodies. Other mature B cell lymphoproliferative disorders examined (PLL, CLL and multiple myeloma) did not express c-fms. We also examined the c-fms expression of normal B-cells: both the in vivo activated (low density) fraction of tonsil B cells and tonsil B cells activated in vitro with SAC plus IL-2 expressed the c-fms protein. As in the case of monocytes c-fms expression by HCs was shown to be down regulated by its ligand M-CSF, and by TNF alpha, both caused a decrease in the receptor expression from 80% to 30% and in the intensity of staining from 6 to 3 x 10(4) molecules/cell. However, as for monocytes, GM-CSF treatment of HCs had no effect on the expression of c-fms; alpha IFN also had no effect. M-CSF treatment of HCs also induced phosphorylation of c-fms, and a number of other proteins, on tyrosine. However, M-CSF was unable to induce HC proliferation either alone or in combination with IL-2, IL-4 or IL-6; in addition it had no effect on HC proliferation induced by SAC, anti-mu or TNF alpha. In addition, M-CSF either alone, or in combination with the above cytokines, had no effect on the differentiated state of HCs as shown by both immunoglobulin secretion and surface antigen expression. M-CSF also had no effect on the morphology or long-term survival of HCs in culture. This study therefore demonstrates that both HCs and activated B-cells express c-fms, and that M-CSF binds to and activates its receptor on HCs. Although c-fms and several other proteins were shown to be phosphorylated in response to M-CSF, the functional consequences of this phosphorylation remain unclear.
authors.affiliation: Department of Haematology, University of Liverpool.
authors.forename: K J
authors.initials: KJ
authors.lastname: Till
authors.forename: A
authors.initials: A
authors.lastname: Lopez
authors.forename: J
authors.initials: J
authors.lastname: Slupsky
authors.forename: J C
authors.initials: JC
authors.lastname: Cawley
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor