title: Human NK cell development requires CD56-mediated motility and formation of the developmental synapse.
abstract: While distinct stages of natural killer (NK) cell development have been defined, the molecular interactions that shape human NK cell maturation are poorly understood. Here we define intercellular interactions between developing NK cells and stromal cells which, through contact-dependent mechanisms, promote the generation of mature, functional human NK cells from CD34(+) precursors. We show that developing NK cells undergo unique, developmental stage-specific sustained and transient interactions with developmentally supportive stromal cells, and that the relative motility of NK cells increases as they move through development in vitro and ex vivo. These interactions include the formation of a synapse between developing NK cells and stromal cells, which we term the developmental synapse. Finally, we identify a role for CD56 in developmental synapse structure, NK cell motility and NK cell development. Thus, we define the developmental synapse leading to human NK cell functional maturation.
authors.affiliation: Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Mace
authors.affiliation: Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.|Immunology Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Justin T
authors.initials: JT
authors.lastname: Gunesch
authors.affiliation: Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.|Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005, USA.
authors.forename: Amera
authors.initials: A
authors.lastname: Dixon
authors.affiliation: Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D019002:CD56 Antigen / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D019061:src-Family Kinases
chemical_list: D019138:Antibodies, Blocking; D019002:CD56 Antigen; D019087:Selectins; D019061:src-Family Kinases