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Record W1973389611 · doi:10.1073/pnas.1102600108

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

2011· article· en· W1973389611 on OpenAlexafffund
Greta Meyers, Yen-Shing Ng, Jason M. Bannock, Aubert Lavoie, Jolán E. Walter, Luigi D. Notarangelo, Sara Şebnem Kılıç, Güzide Aksu, Marianne Debré, Frédéric Rieux‐Laucat, Mary Ellen Conley, Charlotte Cunningham‐Rundles, Anne Durandy, Eric Meffre

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2011
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunodeficiency and Autoimmune Disorders
Canadian institutionsCentre hospitalier de l'Université Laval
FundersNational Institutes of HealthInstitut National de la Santé et de la Recherche MédicaleNational Institute of Allergy and Infectious DiseasesUniversité Laval
KeywordsSomatic hypermutationCytidine deaminaseActivation-induced (cytidine) deaminaseImmunoglobulin class switchingImmunologyAntibodyB cellBiologyImmune tolerancePeripheral toleranceImmune systemCytidineAutoimmunityEnzyme

Abstract

fetched live from OpenAlex

Impaired 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 class-switch 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.058
GPT teacher head0.287
Teacher spread0.229 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations131
Published2011
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicImmunodeficiency and Autoimmune DisordersFrench-language works237,207