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An essential role for the Zn2+ transporter ZIP7 in B cell development.
Anzilotti, Consuelo; Swan, David J; Boisson, Bertrand; Deobagkar-Lele, Mukta; Oliveira, Catarina; Chabosseau, Pauline; Engelhardt, Karin R; Xu, Xijin; Chen, Rui; Alvarez, Luis; Berlinguer-Palmini, Rolando; Bull, Katherine R; Cawthorne, Eleanor; Cribbs, Adam P; Crockford, Tanya L; Dang, Tarana Singh; Fearn, Amy; Fenech, Emma J; de Jong, Sarah J; Lagerholm, B Christoffer; Ma, Cindy S; Sims, David; van den Berg, Bert; Xu, Yaobo; Cant, Andrew J; Kleiner, Gary; Leahy, T Ronan; de la Morena, M Teresa; Puck, Jennifer M; Shapiro, Ralph S; van der Burg, Mirjam; Chapman, J Ross; Christianson, John C; Davies, Benjamin; McGrath, John A; Przyborski, Stefan; Santibanez Koref, Mauro; Tangye, Stuart G; Werner, Andreas; Rutter, Guy A; Padilla-Parra, Sergi; Casanova, Jean-Laurent; Cornall, Richard J; Conley, Mary Ellen; Hambleton, Sophie.
Afiliación
  • Anzilotti C; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Swan DJ; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Boisson B; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Deobagkar-Lele M; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U1163 Necker Hospital for Sick Children, Paris, France.
  • Oliveira C; Paris Descartes University, Imagine Institute, Paris, France.
  • Chabosseau P; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Engelhardt KR; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Xu X; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
  • Chen R; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Alvarez L; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Berlinguer-Palmini R; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Bull KR; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Cawthorne E; Bioimaging Unit, Newcastle University Medical School, Newcastle upon Tyne, UK.
  • Cribbs AP; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Crockford TL; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Dang TS; MRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Fearn A; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Fenech EJ; Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • de Jong SJ; Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
  • Lagerholm BC; Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK.
  • Ma CS; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Sims D; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • van den Berg B; Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
  • Xu Y; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Darlinghurst, New South Wales, Australia.
  • Cant AJ; MRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Kleiner G; Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
  • Leahy TR; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • de la Morena MT; Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Puck JM; Pediatric Allergy and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Shapiro RS; Paediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
  • van der Burg M; Division of Immunology, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
  • Chapman JR; Department of Pediatrics, Division of Allergy, Immunology, and Blood and Bone Marrow Transplantation, University of California, San Francisco, CA, USA.
  • Christianson JC; UCSF Benioff Children's Hospital, San Francisco, CA, USA.
  • Davies B; Midwest Immunology Clinic, Plymouth, MN, USA.
  • McGrath JA; Department of Immunology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
  • Przyborski S; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Santibanez Koref M; Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK.
  • Tangye SG; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Werner A; St John's Institute of Dermatology, King's College London, London, UK.
  • Rutter GA; Department of Biosciences, Durham University, Durham, UK.
  • Padilla-Parra S; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Casanova JL; Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
  • Cornall RJ; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Darlinghurst, New South Wales, Australia.
  • Conley ME; Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, UK.
  • Hambleton S; Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College, London, UK.
Nat Immunol ; 20(3): 350-361, 2019 03.
Article en En | MEDLINE | ID: mdl-30718914
ABSTRACT
Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn2+ in modulating B cell receptor signal strength and positive selection.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Zinc / Linfocitos B / Proteínas de Transporte de Catión / Agammaglobulinemia Tipo de estudio: Prognostic_studies Límite: Animals / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2019 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Zinc / Linfocitos B / Proteínas de Transporte de Catión / Agammaglobulinemia Tipo de estudio: Prognostic_studies Límite: Animals / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2019 Tipo del documento: Article