A CD34+ human cell line model of myeloid dendritic cell differentiation: evidence for a CD14+CD11b+ Langerhans cell precursor

• Published in: Journal of leukocyte biology Vol. 80; no. 6; pp. 1337 - 1344
• Main Authors: Santegoets, Saskia J. A. M., Masterson, Allan J., Sluis, Pieter C., Lougheed, Sinéad M., Fluitsma, Donna M., Eertwegh, Alfons J. M., Pinedo, Herbert M., Scheper, Rik J., Gruijl, Tanja D.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.12.2006
• Subjects: acute myeloid leukemia; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, CD34 - immunology; Antigens, CD34 - metabolism; CD11b Antigen - immunology; CD11b Antigen - metabolism; Cell Differentiation - immunology; Cell Line, Tumor; Cell Proliferation; cytokines; Cytoplasmic Granules - immunology; Cytoplasmic Granules - metabolism; Gene Expression Regulation - immunology; Humans; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lectins, C-Type - biosynthesis; Lectins, C-Type - immunology; Lipopolysaccharide Receptors - immunology; Lipopolysaccharide Receptors - metabolism; Mannose-Binding Lectins - biosynthesis; Mannose-Binding Lectins - immunology; Models, Immunological; MUTZ‐3; Myeloid Progenitor Cells - immunology; Myeloid Progenitor Cells - metabolism; progenitor
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0206111

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+CD11bhi progeny. These CD14+CD11bhi 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.