Salomé Glauzy1, Joel Sng1, Jason M Bannock1, Jacques-Eric Gottenberg2, Anne-Sophie Korganow3, Patrice Cacoub4, David Saadoun4, Eric Meffre1. 1. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut. 2. Strasbourg University Hospital, National Reference Center for Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg and CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence MEDALIS, Strasbourg, France. 3. CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence MEDALIS, UFR Médecine, Université de Strasbourg, and Department of Clinical Immunology and Internal Medicine, National Reference Center for Autoimmune Diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 4. Sorbonne Universités, UPMC Université, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department, INSERM, UMR S959, CNRS, FRE3632, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, National Reference Center for Autoimmune and Autoinflammatory Diseases, Paris, France.
Abstract
OBJECTIVE: Central and peripheral B cell tolerance checkpoints are defective in many patients with autoimmune diseases, but the functionality of each discrete checkpoint has not been assessed in patients with Sjögren's syndrome (SS). We undertook this study to assess this functionality in SS patients. METHODS: Using a polymerase chain reaction-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD19+CD21low CD10+IgMhigh CD27- newly emigrant/transitional B cells and CD19+CD21+CD10-IgM+CD27- mature naive B cells from 5 SS patients. RESULTS: We found that the frequencies of newly emigrant/transitional B cells expressing polyreactive antibodies were significantly increased in SS patients compared to those in healthy donors, revealing defective central B cell tolerance in SS patients. Frequencies of mature naive B cells expressing autoreactive antibodies were also significantly increased in SS patients, thereby illustrating an impaired peripheral B cell tolerance checkpoint in these patients. CONCLUSION: Defective counterselection of developing autoreactive B cells observed in SS patients is a feature common to many other autoimmune diseases and may favor the development of autoimmunity by allowing autoreactive B cells to present self antigens to T cells.
OBJECTIVE: Central and peripheral B cell tolerance checkpoints are defective in many patients with autoimmune diseases, but the functionality of each discrete checkpoint has not been assessed in patients with Sjögren's syndrome (SS). We undertook this study to assess this functionality in SS patients. METHODS: Using a polymerase chain reaction-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD19+CD21low CD10+IgMhigh CD27- newly emigrant/transitional B cells and CD19+CD21+CD10-IgM+CD27- mature naive B cells from 5 SS patients. RESULTS: We found that the frequencies of newly emigrant/transitional B cells expressing polyreactive antibodies were significantly increased in SS patients compared to those in healthy donors, revealing defective central B cell tolerance in SS patients. Frequencies of mature naive B cells expressing autoreactive antibodies were also significantly increased in SS patients, thereby illustrating an impaired peripheral B cell tolerance checkpoint in these patients. CONCLUSION: Defective counterselection of developing autoreactive B cells observed in SS patients is a feature common to many other autoimmune diseases and may favor the development of autoimmunity by allowing autoreactive B cells to present self antigens to T cells.
Authors: Janne Ø Bohnhorst; Marie B Bjørgan; Jørn E Thoen; Roland Jonsson; Jacob B Natvig; Keith M Thompson Journal: Clin Immunol Date: 2002-04 Impact factor: 3.969
Authors: C Vitali; S Bombardieri; R Jonsson; H M Moutsopoulos; E L Alexander; S E Carsons; T E Daniels; P C Fox; R I Fox; S S Kassan; S R Pillemer; N Talal; M H Weisman Journal: Ann Rheum Dis Date: 2002-06 Impact factor: 19.103
Authors: D Saadoun; B Terrier; J Bannock; T Vazquez; C Massad; I Kang; F Joly; M Rosenzwajg; D Sene; P Benech; L Musset; D Klatzmann; E Meffre; P Cacoub Journal: Arthritis Rheum Date: 2013-04
Authors: M Ittah; J-E Gottenberg; A Proust; E Hachulla; X Puechal; P Loiseau; X Mariette; C Miceli-Richard Journal: Genes Immun Date: 2005-08 Impact factor: 2.676
Authors: S S Kassan; T L Thomas; H M Moutsopoulos; R Hoover; R P Kimberly; D R Budman; J Costa; J L Decker; T M Chused Journal: Ann Intern Med Date: 1978-12 Impact factor: 25.391
Authors: Arne Hansen; Marcus Odendahl; Karin Reiter; Annett M Jacobi; Eugen Feist; Jürgen Scholze; Gerd R Burmester; Peter E Lipsky; Thomas Dörner Journal: Arthritis Rheum Date: 2002-08
Authors: Tuure Kinnunen; Nicolas Chamberlain; Henner Morbach; Tineke Cantaert; Megan Lynch; Paula Preston-Hurlburt; Kevan C Herold; David A Hafler; Kevin C O'Connor; Eric Meffre Journal: J Clin Invest Date: 2013-05-15 Impact factor: 14.808
Authors: Elizabeth Cotzomi; Panos Stathopoulos; Casey S Lee; Alanna M Ritchie; John N Soltys; Fabien R Delmotte; Tyler Oe; Joel Sng; Ruoyi Jiang; Anthony K Ma; Jason A Vander Heiden; Steven H Kleinstein; Michael Levy; Jeffrey L Bennett; Eric Meffre; Kevin C O'Connor Journal: Brain Date: 2019-06-01 Impact factor: 13.501
Authors: Salomé Glauzy; Marco Boccitto; Jason M Bannock; Fabien R Delmotte; David Saadoun; Patrice Cacoub; John A Ice; Kathy L Sivils; Judith A James; Sandra L Wolin; Eric Meffre Journal: Arthritis Rheumatol Date: 2018-01-18 Impact factor: 10.995
Authors: Kevin S Cashman; Scott A Jenks; Matthew C Woodruff; Deepak Tomar; Christopher M Tipton; Christopher D Scharer; F Eun-Hyung Lee; Jeremy M Boss; Iñaki Sanz Journal: Immunol Rev Date: 2019-11-22 Impact factor: 12.988
Authors: Sara Tellefsen; Mathias Kaurstad Morthen; Stephen M Richards; Scott M Lieberman; Raheleh Rahimi Darabad; Wendy R Kam; David A Sullivan Journal: Invest Ophthalmol Vis Sci Date: 2018-11-01 Impact factor: 4.799