دورية أكاديمية
أعرض في EDS

Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet + B cells.

التفاصيل البيبلوغرافية
العنوان: Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet + B cells.
المؤلفون: Csomos K; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA. kcsomos@usf.edu., Ujhazi B; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Blazso P; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.; Department of Pediatrics, University of Szeged, Szeged, Hungary., Herrera JL; Cancer and Blood Disorders Institute and Department of Surgery, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Tipton CM; Department of Medicine, Division of Rheumatology, Emory University, Atlanta, GA, USA., Kawai T; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA., Gordon S; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Ellison M; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Wu K; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Stowell M; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Haynes L; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Cruz R; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Zakota B; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Nguyen J; Department of Pathology & Laboratory Medicine, Johns Hopkins All Children's Hospital, St Petersburg, FL, USA., Altrich M; Eurofins Viracor Laboratories, Lee Summit's, MO, USA., Geier CB; Immunology Outpatient Clinic, Vienna, Austria., Sharapova S; Belarusian Research Center for Pediatric Oncology, Minsk, Belarus., Dasso JF; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Leiding JW; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Smith G; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Al-Herz W; Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait., de Barros Dorna M; Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil., Fadugba O; Division of Pulmonary, Allergy and Critical Care, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA., Fronkova E; Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Kanderova V; Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Svaton M; Childhood Leukemia Investigation Prague, Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic., Henrickson SE; Allergy Immunology Division, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Institute for Immunology, the University of Pennsylvania, Philadelphia, PA, USA., Hernandez JD; Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, CA, USA., Kuijpers T; Deptartment of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands., Kandilarova SM; Department of Clinical Immunology, University Hospital Alexandrovska, Medical University, Sofia, Bulgaria., Naumova E; Department of Clinical Immunology, University Hospital Alexandrovska, Medical University, Sofia, Bulgaria., Milota T; Department of Immunology, Second Faculty of Medicine Charles University and University Hospital Motol, Prague, Czech Republic., Sediva A; Department of Immunology, Second Faculty of Medicine Charles University and University Hospital Motol, Prague, Czech Republic., Moshous D; Université de Paris, Paris, France.; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Université Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Laboratory of Genome Dynamics in the Immune System, INSERM UMR1163, Institut Imagine, Paris, France., Neven B; Université de Paris, Paris, France.; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Université Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR1163, Institut Imagine, Paris, France., Saco T; Windom Allergy, Asthma and Sinus, Sarasota, FL, USA., Sargur R; Department of Immunology and Allergy, Sheffield Teaching Hospitals, Sheffield, UK., Savic S; Department of Clinical Immunology and Allergy, St James's University Hospital, Leeds, UK.; National Institute for Health Research-Leeds Musculoskeletal Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine, St James's University Hospital, Leeds, UK., Sleasman J; Division of Allergy, Immunology and Pulmonary Medicine, Duke University School of Medicine, Durham, NC, USA., Sunkersett G; Cancer and Blood Disorder Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA., Ward BR; Division of Allergy and Immunology, Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, USA., Komatsu M; Cancer and Blood Disorders Institute and Department of Surgery, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.; Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Pittaluga S; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Kumanovics A; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Butte MJ; Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics and Jeffrey Modell Diagnostic and Research Center, University of California, Los Angeles, Los Angeles, CA, USA., Cancro MP; Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA., Pillai S; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of technology and Harvard University, Cambridge, MA, USA., Meffre E; Department of Immunobiology, Yale University, New Haven, CT, USA.; Section of Rheumatology, Allergy and Clinical Immunology, Yale School of Medicine, New Haven, CT, USA., Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA., Walter JE; Division of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA. jolanwalter@usf.edu.; Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA, USA. jolanwalter@usf.edu.
المصدر: Nature immunology [Nat Immunol] 2022 Aug; Vol. 23 (8), pp. 1256-1272. Date of Electronic Publication: 2022 Jul 28.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
اللغة: English
بيانات الدورية: Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature America Inc. c2000-
مواضيع طبية MeSH: B-Lymphocytes* , DNA-Binding Proteins*/deficiency , DNA-Binding Proteins*/genetics , Homeodomain Proteins*/genetics , Nuclear Proteins*/deficiency, Cell Differentiation ; Humans ; Immune Tolerance ; Lymphocyte Count
مستخلص: The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.
(© 2022. The Author(s).)
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معلومات مُعتمدة: R01 AI153830 United States AI NIAID NIH HHS; K08 AI103035 United States AI NIAID NIH HHS; ZIA AI001222 United States ImNIH Intramural NIH HHS; P01 AI061093 United States AI NIAID NIH HHS; R01 AI100887 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (DNA-Binding Proteins)
0 (Homeodomain Proteins)
0 (Nuclear Proteins)
0 (RAG2 protein, human)
128559-51-3 (RAG-1 protein)
تواريخ الأحداث: Date Created: 20220728 Date Completed: 20220809 Latest Revision: 20220902
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9355881
DOI: 10.1038/s41590-022-01271-6
PMID: 35902638
قاعدة البيانات: MEDLINE
الوصف
تدمد:1529-2916
DOI:10.1038/s41590-022-01271-6