Evidence map›Paper›PMID 41292746›Full record

ArticlebioRxiv : the preprint server for biology2025

Antibody feedback establishes an affinity brake in the germinal center.

Yu Yan, Xuesong Wang, Zhenfei Xie, Daniel L V Bader, Ryan H Lim, Krystal M Ma, Christopher A Cottrell, Jon M Steichen, Liling Xu, Paula Maldonado Villavicencio and 32 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

42 authors.

Yu YanBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Xuesong WangBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Zhenfei XieBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Daniel L V BaderDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ryan H LimLiu Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Krystal M MaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Christopher A CottrellDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jon M SteichenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Liling XuBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Paula Maldonado VillavicencioBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Madhav AkauliyaBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Ja-Hyun KooBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Jacqueline Ming ShenBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Alexandra VernichLiu Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Oleksandr KalyuzhniyDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Joel D AllenConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Ali A AlbowaideyBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Anthony AliceaBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Bingxian ChenBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Erik GeorgesonDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jordan Renae Ellis-PughBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Nushin AlaviDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abigail EspositoBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Hannah NailiBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Nicole PhelpsDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brendon KelleyBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Michael KubitzDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Quynh Anh PhanBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Alessia LiguoriDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Thavaleak PrumBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Ryan TingleDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Danny LuDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Saman EskandarzadehDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Xiaotie LiuBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
John E WarnerBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Stephanie R WeldonBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Sunny HimansuModerna Therapeutics, Cambridge, MA 02139, USA.
Max CrispinConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Usha NairBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
Sophia LiuLiu Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.
William R SchiefDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Facundo D BatistaBatista Lab, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, 02139, USA.

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Gates Foundation INV-007522Gates Foundation INV-008813Gates Foundation INV-009585Gates Foundation INV-034657NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

Recent advances in mRNA vaccine technology have opened the door to novel types of antigen display, but little is yet known as to how B cells recognize and respond to these formats. By delivering an mRNA-LNP encoded membrane-bound immunogen displaying three conserved HIV-1 Envelope (Env) epitopes to knock-in mouse models with B cell receptors (BCRs) of defined affinities, we investigated how epitope-specific competition shapes germinal center (GC) responses. Co-activation of B cells targeting different epitopes did not alter GC kinetics observed in individual activations, but a striking inverse correlation was observed between BCR affinity and GC residence time in either scenario: high-affinity B cells exhibited shorter persistence in GCs, while those with lower affinity to the antigen were maintained. Furthermore, B cells were able to engage in GC reactions at equivalent rates in the presence or absence of clonal lineages binding the same epitope with similar affinities, while higher-affinity clones suppressed lower-affinity counterparts targeting the same epitope. Spatial transcriptomics revealed plasma-like cells within and adjacent to the GC which, together with the detection of early IgG in draining lymph nodes, suggests that local antibody production from these cells may contribute to feedback-driven kinetics. These findings indicate that a self-modulated local antibody feedback loop may act as a "brake" on epitope-specific recognition-dampening further affinity enhancement for high-affinity B cells and facilitating epitope spreading by redirecting the response toward alternative epitopes.

Indexed as

affinity maturationantibody feedbackB cellGerminal Center

Identifiers

PMID41292746
PMCPMC12642504

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.