title: Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation.
abstract: The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220- NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.
authors.affiliation: Department of Microbiology and Immunology, University of Montreal, and Maisonneuve-Rosemont Hospital Research Center, Montreal, QC.
authors.forename: Fanny
authors.initials: F
authors.lastname: Guimont-Desrochers
authors.forename: Geneviève
authors.initials: G
authors.lastname: Boucher
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Dong
authors.forename: Martine
authors.initials: M
authors.lastname: Dupuis
authors.forename: André
authors.initials: A
authors.lastname: Veillette
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lesage
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis
chemical_list: D007372:Interferons; D017493:Leukocyte Common Antigens