title: A CD34(+) human cell line model of myeloid dendritic cell differentiation: evidence for a CD14(+)CD11b(+) Langerhans cell precursor.
abstract: The study of early events in dendritic cell (DC) differentiation is hampered by the lack of homogeneous primary cell systems that allow the study of cytokine-driven, transitional DC differentiation steps. The CD34(+) acute myeloid leukemia cell line MUTZ-3 displays a unique ability to differentiate into interstitial DC (IDC) and Langerhans cells (LC) in a cytokine-dependent manner. Phenotypic characterization revealed MUTZ-3 to consist of three distinct subpopulations. Small CD34(+)CD14(-)CD11b(-) progenitors constitute the proliferative compartment of the cell line with the ability to differentiate through a CD34(-)CD14(-)CD11b(+) stage to ultimately give rise to a morphologically large, nonproliferating CD14(+)CD11b(hi) progeny. These CD14(+)CD11b(hi) cells were identified as common, immediate myeloid DC precursors with the ability to differentiate into LC and IDC, exhibiting characteristic and mutually exclusive expression of Langerin and DC-specific ICAM-grabbing nonintegrin, respectively. The identity of the MUTZ-3-derived LC subset was confirmed further by the presence of Birbeck granules. We conclude that the MUTZ-3 cell line provides a ready and continuous supply of common myeloid precursors, which should facilitate further study of the ontogeny of myeloid DC lineages.
authors.affiliation: VU University Medical Center, De Boelelaan 1117, Amsterdam 1081HV, The Netherlands.
authors.forename: Saskia J A M
authors.initials: SJ
authors.lastname: Santegoets
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Masterson
authors.forename: Pieter C
authors.initials: PC
authors.lastname: van der Sluis
authors.forename: Sinéad M
authors.initials: SM
authors.lastname: Lougheed
authors.forename: Donna M
authors.initials: DM
authors.lastname: Fluitsma
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000276:immunology; D018448:Models, Immunological; D023461:Myeloid Progenitor Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D039481:CD11b Antigen; C121916:CD207 protein, human; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D037241:Mannose-Binding Lectins