Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0206111 on September 7, 2006

Published online before print September 7, 2006
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(Journal of Leukocyte Biology. 2006;80:1337-1344.)
© 2006 by Society for Leukocyte Biology

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

Saskia J. A. M. Santegoets*,1, Allan J. Masterson{dagger},1, Pieter C. van der Sluis*, Sinéad M. Lougheed{dagger}, Donna M. Fluitsma{ddagger}, Alfons J. M. van den Eertwegh{dagger}, Herbert M. Pinedo{dagger}, Rik J. Scheper*,2 and Tanja D. de Gruijl{dagger}

* Departments of Pathology,
{dagger} Medical Oncology, and
{ddagger} Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands

2 Correspondence: Department of Pathology, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081HV, The Netherlands. E-mail: rj.scheper{at}vumc.nl

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+CD14CD11b progenitors constitute the proliferative compartment of the cell line with the ability to differentiate through a CD34CD14CD11b+ 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.

Key Words: MUTZ-3 • progenitor • acute myeloid leukemia • cytokines




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