Publication:
Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint

dc.contributor.buuauthorKılıç, Sara Şebnem
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
dc.contributor.orcid0000-0001-8571-2581
dc.contributor.researcheridAAH-1658-2021
dc.contributor.scopusid34975059200
dc.date.accessioned2022-10-11T12:08:35Z
dc.date.available2022-10-11T12:08:35Z
dc.date.issued2016-11
dc.descriptionÇalışmada 27 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır.
dc.description.abstractPatients with mutations in AICDA, which encodes activation-induced cytidine deaminase (AID), display an impaired peripheral B cell tolerance. AID mediates class-switch recombination (CSR) and somatic hypermutation (SHM) in B cells, but the mechanism by which AID prevents the accumulation of autoreactive B cells in blood is unclear. Here, we analyzed B cell tolerance in AID-deficient patients, patients with autosomal dominant AID mutations (AD-AID), asymptomatic AICDA heterozygotes (AID(+/-)), and patients with uracil N-glycosylase (UNG) deficiency, which impairs CSR but not SHM. The low frequency of autoreactive mature naive B cells in-UNG-deficient patients resembled that of healthy subjects, revealing that impaired CSR does not interfere with the peripheral B cell tolerance checkpoint. In contrast, we observed decreased frequencies of SHM in memory B cells from AD-AID patients and AID(+/-) subjects, who were unable to prevent the accumulation of autoreactive mature naive B cells. In addition, the individuals with AICDA mutations, but not UNG-deficient patients, displayed Tregs with defective suppressive capacity that correlated with increases in circulating T follicular helper cells and enhanced cytokine production. We conclude that SHM, but not CSR, regulates peripheral B cell tolerance through the production of mutated antibodies that clear antigens and prevent sustained interleukin secretions that interfere with Treg function.
dc.description.sponsorshipNIH National Institute of Allergy & Infectious Diseases (NIAID)
dc.description.sponsorshipUnited States Department of Health & Human Services - AI071087 - AI082713 - AI095848 - AI061093 - T32 AI089704
dc.description.sponsorshipRubicon Program of the Netherlands Organization for Scientific Research
dc.description.sponsorshipSigrid Juselius Foundation
dc.description.sponsorshipFinnish Medical Foundation
dc.description.sponsorshipSaastamoinen Foundation
dc.description.sponsorshipJeffrey Modell Foundation
dc.description.sponsorshipUnited States Department of Health & Human Services - UL1TR001863
dc.description.sponsorshipNational Institutes of Health (NIH) - USA
dc.description.sponsorshipNIH National Center for Advancing Translational Sciences (NCATS) - U19AI082713 - R01AI071087 - P01AI061093 - R21AI095848 - T32AI089704
dc.description.sponsorshipNIH National Institute of Allergy & Infectious Diseases (NIAID)
dc.identifier.citationCantaert, T. vd. (2016). "Decreased somatic hypermutaton induces an impaired peripheral B cell tolerance checkpoint". Journal of Clinical Investigation, 126(11), 4289-4302.
dc.identifier.endpage4302
dc.identifier.issn0021-9738
dc.identifier.issn1558-8238
dc.identifier.issue11
dc.identifier.pubmed27701145
dc.identifier.scopus2-s2.0-84994643712
dc.identifier.startpage4289
dc.identifier.urihttps://doi.org/10.1172/JCI84645
dc.identifier.urihttps://www.jci.org/articles/view/84645
dc.identifier.urihttp://hdl.handle.net/11452/29051
dc.identifier.volume126
dc.identifier.wos000386992900020
dc.indexed.scopusScopus
dc.indexed.wosSCIE
dc.language.isoen
dc.publisherAmerican Society for Clinical Investigation
dc.relation.collaborationYurt dışı
dc.relation.collaborationSanayi
dc.relation.journalJournal of Clinical Investigation
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectResearch & experimental medicine
dc.subjectInduced cytidine deaminase
dc.subjectClass-switch recombination
dc.subjectHyper-igm syndrome
dc.subjectSystemic-lupus-erythematosus
dc.subjectRegulatory T-cells
dc.subjectMemory B
dc.subjectAntibody-responses
dc.subjectCD40 ligand
dc.subjectActivation
dc.subjectAid
dc.subject.emtreeActivation induced cytidine deaminase
dc.subject.emtreeGamma interferon
dc.subject.emtreeInterleukin 10
dc.subject.emtreeInterleukin 17
dc.subject.emtreeInterleukin 2
dc.subject.emtreeInterleukin 6
dc.subject.emtreeUracil
dc.subject.emtreeAICDA (activation-induced cytidine deaminase)
dc.subject.emtreeCytidine deaminase
dc.subject.emtreeAntibody production
dc.subject.emtreeArticle
dc.subject.emtreeAutosomal dominant inheritance
dc.subject.emtreeB lymphocyte
dc.subject.emtreeCell proliferation
dc.subject.emtreeControlled study
dc.subject.emtreeCytokine production
dc.subject.emtreeHuman
dc.subject.emtreeHuman experiment
dc.subject.emtreeImmunological tolerance
dc.subject.emtreeMemory cell
dc.subject.emtreeNormal human
dc.subject.emtreePeripheral blood mononuclear cell
dc.subject.emtreePriority journal
dc.subject.emtreeRegulatory T lymphocyte
dc.subject.emtreeSomatic hypermutation
dc.subject.emtreeB lymphocyte
dc.subject.emtreeCell cycle checkpoint
dc.subject.emtreeDeficiency
dc.subject.emtreeFemale
dc.subject.emtreeGenetics
dc.subject.emtreeImmunological memory
dc.subject.emtreeImmunology
dc.subject.emtreeMale
dc.subject.emtreeMutation
dc.subject.emtreePathology
dc.subject.emtreeSomatic hypermutation
dc.subject.meshB-Lymphocytes
dc.subject.meshCell cycle checkpoints
dc.subject.meshCytidine deaminase
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshImmune tolerance
dc.subject.meshImmunologic memory
dc.subject.meshMale
dc.subject.meshMutation
dc.subject.meshSomatic hypermutation, immunoglobulin
dc.subject.meshT-Lymphocytes, regulatory
dc.subject.scopusAICDA (Activation-induced Cytidine Deaminase); Cytidine Deaminase; DNA
dc.subject.wosMedicine, research & experimental
dc.titleDecreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint
dc.typeArticle
dc.wos.quartileQ1
dc.wos.quartileQ1
dspace.entity.typePublication
local.contributor.departmentTıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
local.indexed.atPubMed
local.indexed.atWOS
local.indexed.atScopus

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