Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations
Summary: Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incomplet...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004576 |
| _version_ | 1797837069995737088 |
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| author | Vanda Friman Isabella Quinti Alexey N. Davydov Mikhail Shugay Chiara Farroni Erik Engström Shirin Pour Akaber Sabina Barresi Ahmed Mohamed Federica Pulvirenti Cinzia Milito Guido Granata Ezio Giorda Sara Ahlström Johanna Karlsson Emiliano Marasco Valentina Marcellini Chiara Bocci Simona Cascioli Marco Scarsella Ganesh Phad Andreas Tilevik Marco Tartaglia Mats Bemark Dmitriy M. Chudakov Rita Carsetti Ola Grimsholm |
| author_facet | Vanda Friman Isabella Quinti Alexey N. Davydov Mikhail Shugay Chiara Farroni Erik Engström Shirin Pour Akaber Sabina Barresi Ahmed Mohamed Federica Pulvirenti Cinzia Milito Guido Granata Ezio Giorda Sara Ahlström Johanna Karlsson Emiliano Marasco Valentina Marcellini Chiara Bocci Simona Cascioli Marco Scarsella Ganesh Phad Andreas Tilevik Marco Tartaglia Mats Bemark Dmitriy M. Chudakov Rita Carsetti Ola Grimsholm |
| author_sort | Vanda Friman |
| collection | DOAJ |
| description | Summary: Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity. |
| first_indexed | 2024-04-09T15:19:59Z |
| format | Article |
| id | doaj.art-03982c683b2d450cbf5de2b91419aa00 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T15:19:59Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-03982c683b2d450cbf5de2b91419aa002023-04-29T14:49:35ZengElsevierCell Reports2211-12472023-05-01425112446Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestationsVanda Friman0Isabella Quinti1Alexey N. Davydov2Mikhail Shugay3Chiara Farroni4Erik Engström5Shirin Pour Akaber6Sabina Barresi7Ahmed Mohamed8Federica Pulvirenti9Cinzia Milito10Guido Granata11Ezio Giorda12Sara Ahlström13Johanna Karlsson14Emiliano Marasco15Valentina Marcellini16Chiara Bocci17Simona Cascioli18Marco Scarsella19Ganesh Phad20Andreas Tilevik21Marco Tartaglia22Mats Bemark23Dmitriy M. Chudakov24Rita Carsetti25Ola Grimsholm26Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyCentral European Institute of Technology, Brno, Czech RepublicCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, RussiaTranslational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), Rome, Italy; B Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, ItalyDepartment of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenInstitute of Pathophysiology and Allergy Research, Centre for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, AustriaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, ItalyDepartment of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandCentre for Primary Immune Deficiency, AUO Policlinico Umberto I, Rome, ItalyDepartment of Molecular Medicine, Sapienza University of Rome, Rome, ItalyClinical and Research Department for Infectious Diseases, National Institute for Infectious Diseases L. Spallanzani (IRCCS), 00149 Rome, ItalyResearch Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, ItalyDepartment of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDivision of Rheumatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, ItalyResearch Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, ItalyB Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, ItalyResearch Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, ItalyResearch Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, ItalyInstitute for Research in Biomedicine (IRB), Università della Svizzera Italiana (USI), Bellinzona, SwitzerlandSchool of Bioscience, University of Skövde, Skövde, SwedenGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, ItalyDepartment of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Immunology and Transfusion Medicine, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, SwedenCenter of Life Sciences, Skolkovo Institute of Science and Technology, Moscow, Russia; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia; Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russia; Central European Institute of Technology, Brno, Czech RepublicB Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy; Unit of Diagnostic Immunology, Department of Laboratories, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, ItalyInstitute of Pathophysiology and Allergy Research, Centre for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria; Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; B Cell Pathophysiology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy; Corresponding authorSummary: Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity.http://www.sciencedirect.com/science/article/pii/S2211124723004576CP: Immunology |
| spellingShingle | Vanda Friman Isabella Quinti Alexey N. Davydov Mikhail Shugay Chiara Farroni Erik Engström Shirin Pour Akaber Sabina Barresi Ahmed Mohamed Federica Pulvirenti Cinzia Milito Guido Granata Ezio Giorda Sara Ahlström Johanna Karlsson Emiliano Marasco Valentina Marcellini Chiara Bocci Simona Cascioli Marco Scarsella Ganesh Phad Andreas Tilevik Marco Tartaglia Mats Bemark Dmitriy M. Chudakov Rita Carsetti Ola Grimsholm Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations Cell Reports CP: Immunology |
| title | Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations |
| title_full | Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations |
| title_fullStr | Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations |
| title_full_unstemmed | Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations |
| title_short | Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations |
| title_sort | defective peripheral b cell selection in common variable immune deficiency patients with autoimmune manifestations |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723004576 |
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