Publication: Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint
dc.contributor.buuauthor | Kılıç, Sara Şebnem | |
dc.contributor.department | Tıp Fakültesi | |
dc.contributor.department | Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı | |
dc.contributor.orcid | 0000-0001-8571-2581 | |
dc.contributor.researcherid | AAH-1658-2021 | |
dc.contributor.scopusid | 34975059200 | |
dc.date.accessioned | 2022-10-11T12:08:35Z | |
dc.date.available | 2022-10-11T12:08:35Z | |
dc.date.issued | 2016-11 | |
dc.description | Çalışmada 27 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. | |
dc.description.abstract | Patients 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.sponsorship | NIH National Institute of Allergy & Infectious Diseases (NIAID) | |
dc.description.sponsorship | United States Department of Health & Human Services - AI071087 - AI082713 - AI095848 - AI061093 - T32 AI089704 | |
dc.description.sponsorship | Rubicon Program of the Netherlands Organization for Scientific Research | |
dc.description.sponsorship | Sigrid Juselius Foundation | |
dc.description.sponsorship | Finnish Medical Foundation | |
dc.description.sponsorship | Saastamoinen Foundation | |
dc.description.sponsorship | Jeffrey Modell Foundation | |
dc.description.sponsorship | United States Department of Health & Human Services - UL1TR001863 | |
dc.description.sponsorship | National Institutes of Health (NIH) - USA | |
dc.description.sponsorship | NIH National Center for Advancing Translational Sciences (NCATS) - U19AI082713 - R01AI071087 - P01AI061093 - R21AI095848 - T32AI089704 | |
dc.description.sponsorship | NIH National Institute of Allergy & Infectious Diseases (NIAID) | |
dc.identifier.citation | Cantaert, T. vd. (2016). "Decreased somatic hypermutaton induces an impaired peripheral B cell tolerance checkpoint". Journal of Clinical Investigation, 126(11), 4289-4302. | |
dc.identifier.endpage | 4302 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.issn | 1558-8238 | |
dc.identifier.issue | 11 | |
dc.identifier.pubmed | 27701145 | |
dc.identifier.scopus | 2-s2.0-84994643712 | |
dc.identifier.startpage | 4289 | |
dc.identifier.uri | https://doi.org/10.1172/JCI84645 | |
dc.identifier.uri | https://www.jci.org/articles/view/84645 | |
dc.identifier.uri | http://hdl.handle.net/11452/29051 | |
dc.identifier.volume | 126 | |
dc.identifier.wos | 000386992900020 | |
dc.indexed.scopus | Scopus | |
dc.indexed.wos | SCIE | |
dc.language.iso | en | |
dc.publisher | American Society for Clinical Investigation | |
dc.relation.collaboration | Yurt dışı | |
dc.relation.collaboration | Sanayi | |
dc.relation.journal | Journal of Clinical Investigation | |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Research & experimental medicine | |
dc.subject | Induced cytidine deaminase | |
dc.subject | Class-switch recombination | |
dc.subject | Hyper-igm syndrome | |
dc.subject | Systemic-lupus-erythematosus | |
dc.subject | Regulatory T-cells | |
dc.subject | Memory B | |
dc.subject | Antibody-responses | |
dc.subject | CD40 ligand | |
dc.subject | Activation | |
dc.subject | Aid | |
dc.subject.emtree | Activation induced cytidine deaminase | |
dc.subject.emtree | Gamma interferon | |
dc.subject.emtree | Interleukin 10 | |
dc.subject.emtree | Interleukin 17 | |
dc.subject.emtree | Interleukin 2 | |
dc.subject.emtree | Interleukin 6 | |
dc.subject.emtree | Uracil | |
dc.subject.emtree | AICDA (activation-induced cytidine deaminase) | |
dc.subject.emtree | Cytidine deaminase | |
dc.subject.emtree | Antibody production | |
dc.subject.emtree | Article | |
dc.subject.emtree | Autosomal dominant inheritance | |
dc.subject.emtree | B lymphocyte | |
dc.subject.emtree | Cell proliferation | |
dc.subject.emtree | Controlled study | |
dc.subject.emtree | Cytokine production | |
dc.subject.emtree | Human | |
dc.subject.emtree | Human experiment | |
dc.subject.emtree | Immunological tolerance | |
dc.subject.emtree | Memory cell | |
dc.subject.emtree | Normal human | |
dc.subject.emtree | Peripheral blood mononuclear cell | |
dc.subject.emtree | Priority journal | |
dc.subject.emtree | Regulatory T lymphocyte | |
dc.subject.emtree | Somatic hypermutation | |
dc.subject.emtree | B lymphocyte | |
dc.subject.emtree | Cell cycle checkpoint | |
dc.subject.emtree | Deficiency | |
dc.subject.emtree | Female | |
dc.subject.emtree | Genetics | |
dc.subject.emtree | Immunological memory | |
dc.subject.emtree | Immunology | |
dc.subject.emtree | Male | |
dc.subject.emtree | Mutation | |
dc.subject.emtree | Pathology | |
dc.subject.emtree | Somatic hypermutation | |
dc.subject.mesh | B-Lymphocytes | |
dc.subject.mesh | Cell cycle checkpoints | |
dc.subject.mesh | Cytidine deaminase | |
dc.subject.mesh | Female | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Immune tolerance | |
dc.subject.mesh | Immunologic memory | |
dc.subject.mesh | Male | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Somatic hypermutation, immunoglobulin | |
dc.subject.mesh | T-Lymphocytes, regulatory | |
dc.subject.scopus | AICDA (Activation-induced Cytidine Deaminase); Cytidine Deaminase; DNA | |
dc.subject.wos | Medicine, research & experimental | |
dc.title | Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint | |
dc.type | Article | |
dc.wos.quartile | Q1 | |
dc.wos.quartile | Q1 | |
dspace.entity.type | Publication | |
local.contributor.department | Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı | |
local.indexed.at | PubMed | |
local.indexed.at | WOS | |
local.indexed.at | Scopus |