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Record W4389154843 · doi:10.1101/2023.11.28.567094

Pathogenic IgE-fated memory B cell responses retain functional plasticity

2023· preprint· en· W4389154843 on OpenAlexafffund
Kelly Bruton, Allyssa Phelps, Atai Ariaz, Allison Fang, Tina D. Walker, Jianping Wen, Sharon S. Khavkine-Binstock, Olivia Mann-Delany, Niels Peter Hell Knudsen, Siyon Gadkar, Emily Grydziuszko, Joshua F. E. Koenig, Aidan Gagnon, Susan Waserman, Peter S. Andersen, Manel Jordana

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsOttawa Allergy Research Corporation
FundersCanadian Institutes of Health ResearchFood Allergy CanadaMcMaster University
KeywordsGerminal centerBiologyImmunoglobulin EImmunologyInterleukin 4AntibodyCell biologyB cellCytokine

Abstract

fetched live from OpenAlex

Abstract Long-lived immunoglobulin (Ig) E responses against innocuous environmental and dietary antigens (Ags) are maintained by an IgG1-dominant memory B cell (MBC) compartment primed for IL-4 responsiveness. The plasticity of the MBC compartment destined for IgE class switch recombination (CSR), however, remains poorly understood. In this work, we report a critical IL-4/IL-13 dependency for the pathogenic IgE fate of type 2-polarized MBCs. Initiating a recall response in the absence of IL-4/IL-13 signaling diminished the type 2 MBC phenotype in mice and humans and, in mice, permitted the emergence of long-lived Ag-specific IgG2c + MBCs. The divergence to a type 1-like response was dependent on IFN-γ signaling and arose from both unswitched and class-switched Ag-specific B cells in vivo . This reprogrammed fate was sustained even beyond therapeutic intervention, revealing fundamental insight into the plasticity of the allergen-specific MBC response. One Sentence Summary B cell responses to allergens can be reprogrammed away from a pathogenic fate through IL-4/IL-13 signaling blockade.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.019

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0060.003

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 head0.022
GPT teacher head0.209
Teacher spread0.187 · 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 designBench or experimental
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

Citations1
Published2023
Admission routes2
Has abstractyes

Explore more

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