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Published online before print September 7, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0206111

Received for publication February 22, 2006.
Revised June 22, 2006.
Accepted for publication July 24, 2006.

Article

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

Saskia J. A. M. Santegoets ^*, Allan J. Masterson , Pieter C. van der Sluis ^*, Sinéad M. Lougheed , Donna M. Fluitsma , Alfons J. M. van den Eertwegh , Herbert M. Pinedo , Rik J. Scheper ^*@, and Tanja D. de Gruijl

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

^@ To whom correspondence should be addressed. E-mail: rj.scheper{at}vumc.nl.

	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.

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