Evidence map›Paper›PMID 41690309›Full record

ArticleImmunity2026

Local antibody feedback enforces a checkpoint on affinity maturation in the germinal center and promotes epitope spreading.

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 M Villavicencio and 32 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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4 · The record

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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 Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Xuesong WangBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Zhenfei XieBatista Laboratory, 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; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ryan H LimLiu Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Krystal M MaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Liling XuBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Paula M VillavicencioBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Madhav AkauliyaBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Ja-Hyun KooBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Jacqueline Ming ShenBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Alexandra VernichLiu Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, 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; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Ali A AlbowaideyBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Anthony AliceaBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Bingxian ChenBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Liu Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jordan Renae Ellis-PughBatista Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Abigail EspositoBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Hannah NailiBatista Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brendon KelleyBatista Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Quynh Anh PhanBatista Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Thavaleak PrumBatista Laboratory, 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; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Danny LuDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Saman EskandarzadehDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Xiaotie LiuBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
John E WarnerBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Stephanie R WeldonBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Sunny HimansuModerna, Cambridge, MA 02142, USA.
Max CrispinConsortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Usha NairBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA.
Sophia LiuLiu Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: sophia.liu@mgh.harvard.edu.
William R SchiefDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Moderna, Cambridge, MA 02142, USA. Electronic address: schief@scripps.edu.
Facundo D BatistaBatista Laboratory, Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: fbatista1@mgh.harvard.edu.

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
NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

Circulating antibodies from previous immune encounters impact subsequent humoral responses. Here, we investigated how local epitope-specific competition shapes ongoing germinal center (GC) responses by delivering an mRNA-LNP-encoded membrane-bound immunogen displaying three conserved HIV-1 envelope (Env) epitopes to mouse models bearing B cell receptors (BCRs) of defined affinities. High-affinity B cells exhibited shorter GC residency than lower-affinity counterparts. B cells engaged GC reactions at equivalent rates in the presence or absence of clonal lineages binding the same epitope with similar affinities; however, higher-affinity clones suppressed lower-affinity counterparts targeting the same epitope. Spatial transcriptomics revealed plasma-like cells within and adjacent to the GC, and early immunoglobulin G (IgG) was detectable in draining lymph nodes. Our findings suggest that a self-modulating local antibody feedback loop limits epitope-specific recognition-dampening selection for higher-affinity B cells and facilitating epitope spreading by redirecting the response toward alternative epitopes.

Indexed as

Antibody AffinityB-LymphocytesEpitopes, B-LymphocyteGerminal CenterHIV-1Animalsenv Gene Products, Human Immunodeficiency VirusEpitopesFeedback, PhysiologicalHIV AntibodiesHumansImmunoglobulin GMicePlasma CellsReceptors, Antigen, B-Cellenv Gene Products, Human Immunodeficiency VirusEpitopesEpitopes, B-LymphocyteHIV AntibodiesImmunoglobulin GReceptors, Antigen, B-Cellaffinity maturationantibody feedbackB cellgerminal centerHIVlocal antibody poolplasma cellssequential immunizationvaccine

Identifiers

PMID41690309
PMCPMC13189263

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