Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans

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dc.contributor.authorMeyers, Greta
dc.contributor.authorNg, Yen-Shing
dc.contributor.authorBannock, Jason M.
dc.contributor.authorLavoie, Aubert
dc.contributor.authorWalter, Jolan E.
dc.contributor.authorNotarangelo, Luigi D.
dc.contributor.authorKilic, Sara S.
dc.contributor.authorAksu, Guzide
dc.contributor.authorDebre, Marianne
dc.contributor.authorRieux-Laucat, Frederic
dc.contributor.authorConley, Mary Ellen
dc.contributor.authorCunningham-Rundles, Charlotte
dc.contributor.authorDurandy, Anne
dc.contributor.authorMeffre, Eric
dc.date.accessioned2019-10-27T21:37:44Z
dc.date.available2019-10-27T21:37:44Z
dc.date.issued2011
dc.departmentEge Üniversitesien_US
dc.description.abstractImpaired immune functions leading to primary immunodeficiencies often correlate with paradoxical autoimmune complications; patients with hyper-IgM syndromes who are deficient in activation-induced cytidine deaminase (AID), which is required for classs-witch recombination and somatic hypermutation, are prone to develop autoimmune diseases. To investigate the impact of AID-deficiency on early B-cell tolerance checkpoints in humans, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from AID-deficient patients. New emigrant/transitional and mature naive B cells from AID-deficient patients express an abnormal Ig repertoire and high frequencies of autoreactive antibodies, demonstrating that AID is required for the establishment of both central and peripheral B-cell tolerance. In addition, B-cell tolerance was further breached in AID-deficient patients as illustrated by the detection of anti-nuclear IgM antibodies in the serum of all patients. Thus, we identified a major and previously unsuspected role for AID in the removal of developing autoreactive B cells in humans.en_US
dc.description.sponsorshipNational Institutes of Health/National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [AI061093, AI071087, AI082713]; Institut National de la Sante et de la Recherche MedicaleInstitut National de la Sante et de la Recherche Medicale (Inserm); CEE European Primary Antibody Deficiencies [201549]; Association Contre le Canceren_US
dc.description.sponsorshipWe thank Dr. S. Rudchenko and S. Semova for cell sorting, Dr. C. Price for providing CD40L-deficient patient samples, Mrs. M. C. Stolzenberg and M. Forveille for excellent technical assistance, Dr. J. Craft for providing tonsil samples, and Dr. D. Schatz for advice and discussions. We also thank all the members of the Immunodeficiency Clinic of the Centre Hospitalier de l'Universite Laval. This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grants AI061093, AI071087, and AI082713 (to E. M.), Institut National de la Sante et de la Recherche Medicale, CEE European Primary Antibody Deficiencies Contract Seventh Framework Program (201549), and Association Contre le Cancer (F. R.-L. and A.D.).en_US
dc.identifier.doi10.1073/pnas.1102600108en_US
dc.identifier.endpage11559en_US
dc.identifier.issn0027-8424
dc.identifier.issue28en_US
dc.identifier.pmid21700883en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage11554en_US
dc.identifier.urihttps://doi.org/10.1073/pnas.1102600108
dc.identifier.urihttps://hdl.handle.net/11454/46259
dc.identifier.volume108en_US
dc.identifier.wosWOS:000292635200053en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherNatl Acad Sciencesen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleActivation-induced cytidine deaminase (AID) is required for B-cell tolerance in humansen_US
dc.typeArticleen_US

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