title: Acquired somatic mutations in PNH reveal long-term maintenance of adaptive NK cells independent of HSPCs.
abstract: Natural killer (NK) cells have long been considered short-lived effectors of innate immunity. However, recent animal models and human studies suggest that subsets of NK cells have adaptive features. We investigate clonal relationships of various NK-cell subsets, including the adaptive population, by taking advantage of naturally occurring X-linked somaticPIGAmutations in hematopoietic stem and progenitor cells (HSPCs) from patients with paroxysmal nocturnal hemoglobinuria (PNH). The affected HSPCs and their progeny lack expression of glycosylphosphatidylinositol (GPI) anchors on their cell surface, allowing quantification ofPIGA-mutant (GPI-negative) HSPC-derived peripheral blood cell populations. The fraction of GPI-negative cells within the CD56dimNK cells was markedly lower than that of neutrophils and the CD56brightNK-cell compartments. This discrepancy was most prominent within the adaptive CD56dimNK-cell population lacking PLZF expression. The functional properties of these adaptive NK cells were similar in PNH patients and healthy individuals. Our findings support the existence of a long-lived, adaptive NK-cell population maintained independently from GPIposCD56dim.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.|Multidisciplinary Center for Biological Research, University of Campinas, Campinas, Brazil.
authors.forename: Marcus A F
authors.initials: MA
authors.lastname: Corat
authors.affiliation: Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schlums
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and.
authors.forename: Jakob
authors.initials: J
authors.lastname: Theorell
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Espinoza
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Sellers
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Townsley
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.affiliation: Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and.|Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Thomas
authors.initials: T
authors.lastname: Winkler
mesh_terms: D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009844:Oligosaccharides / Q000235:genetics / Q000276:immunology; D000075722:Promyelocytic Leukemia Zinc Finger Protein
chemical_list: C559297:(6-O-aminoethylphosphonato-mannopyranosyl)-(1-2)-mannopyranosyl-(1-6)-mannopyranosyl-(1-4)-(2-amino-2-deoxyglucopyranosyl)-(1-6)-1-O-(1,2-di-O-octadecanoyl-sn-glyceryl-phosphonato)-myo-inositol; D019002:CD56 Antigen; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; C522918:NCAM1 protein, human; D009844:Oligosaccharides; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C080086:phosphatidylinositol glycan-class A protein; C092037:ZBTB16 protein, human