Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/29051
Title: Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint
Authors: Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.
0000-0001-8571-2581
Kılıç, Sara Şebnem
AAH-1658-2021
34975059200
Keywords: Research & experimental medicine
Induced cytidine deaminase
Class-switch recombination
Hyper-igm syndrome
Systemic-lupus-erythematosus
Regulatory T-cells
Memory B
Antibody-responses
CD40 ligand
Activation
Aid
Issue Date: Nov-2016
Publisher: American Society for Clinical Investigation
Citation: Cantaert, T. vd. (2016). "Decreased somatic hypermutaton induces an impaired peripheral B cell tolerance checkpoint". Journal of Clinical Investigation, 126(11), 4289-4302.
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.
Description: Çalışmada 27 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır.
URI: https://doi.org/10.1172/JCI84645
https://www.jci.org/articles/view/84645
http://hdl.handle.net/11452/29051
ISSN: 0021-9738
1558-8238
Appears in Collections:PubMed
Scopus
Web of Science

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