ArticleThe Journal of clinical investigation2016
Decreased somatic hypermutation induces an impaired peripheral B cell tolerance checkpoint.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
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- IgA defects in CVID lead to bacterial translocation, increased serum γ-interferon, and BAFF.Journal of human immunity · 2026Article
- DNA Damage and Repair in Thyroid Physiology and Disease.Endocrine reviews · 2026Review
- Increased IGF-1 and DNA Synthesis in Patients With Activation-Induced Cytidine Deaminase Deficiency.Journal of immunology research · 2026Article
- Balancing functions of regulatory T cells in mosquito-borne viral infections.Emerging microbes & infections · 2024Review
- Article
- A Novel Heterozygous Variant in AICDA Impairs Ig Class Switching and Somatic Hypermutation in Human B Cells and is Associated with Autosomal Dominant HIGM2 Syndrome.Journal of clinical immunology · 2024Article
- Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis.Science translational medicine · 2023Article
- Attempts to evaluate locus suicide recombination and its potential role in B cell negative selection in the mouse.Frontiers in immunology · 2023Article
- Article
- Atypical Autosomal Recessive AID Deficiency-Yet Another Piece of the Hyper-IgM Puzzle.Journal of clinical immunology · 2022Article
- Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen-Specific Clones.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Positive and negative selection shape the human naive B cell repertoire.The Journal of clinical investigation · 2022Article
- Activation induced cytidine deaminase: An old friend with new faces.Frontiers in immunology · 2022Review
- Interleukins 4 and 21 Protect Anti-IgM Induced Cell Death in Ramos B Cells: Implication for Autoimmune Diseases.Frontiers in immunology · 2022Article
- Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function.Blood · 2021Article
- Helper T Cells in Idiopathic Membranous Nephropathy.Frontiers in immunology · 2021Review
- Autoantibody Profiling in Plasma of Dengue Virus-Infected Individuals.Pathogens (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 3 countries.
Funding
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.
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