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Record W4317497423 · doi:10.1126/science.abj7412

<i>BTG1</i> mutation yields supercompetitive B cells primed for malignant transformation

2023· article· en· W4317497423 on OpenAlexafffund
Coraline Mlynarczyk, Matt Teater, Juhee Pae, Christopher R. Chin, Ling Wang, Theinmozhi Arulraj, Darko Barišić, Antonin Papin, Kenneth B. Hoehn, Ekaterina D. Kots, Jonatan Ersching, Arnab Bandyopadhyay, Ersilia Barin, Hui Xian Poh, Chiara M. Evans, Amy Chadburn, Zhengming Chen, Hao Shen, Hannah M. Isles, Benedikt W. Pelzer, Ioanna Tsialta, Ashley S. Doane, Huimin Geng, Muhammad Hassan Rehman, Jonah Melnick, Wyatt Morgan, Diu Nguyen, Olivier Elemento, Michael G. Kharas, Samie R. Jaffrey, David W. Scott, George Khelashvili, Michael Meyer‐Hermann, Gabriel D. Victora, Ari Melnick

Bibliographic record

VenueScience · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related gene regulation
Canadian institutionsSpinal Cord Injury BC
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteDeutsche KrebshilfeNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungAgency for Science, Technology and ResearchDamon Runyon Cancer Research FoundationNational Science FoundationIncyteDeutsche ForschungsgemeinschaftMichael Smith Health Research BCMemorial Sloan-Kettering Cancer CenterCancer Research Institute
KeywordsGerminal centerBiologyMulticellular organismMutationImmune systemAcquired immune systemAntibodyPhenotypeMechanism (biology)LimitingB cellGeneticsGeneImmunologyCancer research

Abstract

fetched live from OpenAlex

Multicellular life requires altruistic cooperation between cells. The adaptive immune system is a notable exception, wherein germinal center B cells compete vigorously for limiting positive selection signals. Studying primary human lymphomas and developing new mouse models, we found that mutations affecting BTG1 disrupt a critical immune gatekeeper mechanism that strictly limits B cell fitness during antibody affinity maturation. This mechanism converted germinal center B cells into supercompetitors that rapidly outstrip their normal counterparts. This effect was conferred by a small shift in MYC protein induction kinetics but resulted in aggressive invasive lymphomas, which in humans are linked to dire clinical outcomes. Our findings reveal a delicate evolutionary trade-off between natural selection of B cells to provide immunity and potentially dangerous features that recall the more competitive nature of unicellular organisms.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.020
Threshold uncertainty score0.262

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.010
GPT teacher head0.262
Teacher spread0.251 · 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 teacher head, 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

Citations41
Published2023
Admission routes2
Has abstractyes

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