Evidence map›Paper›PMID 40661619›Full record

ArticlebioRxiv : the preprint server for biology2025

Replaying germinal center evolution on a quantified affinity landscape.

William S DeWitt, Ashni A Vora, Tatsuya Araki, Jared G Galloway, Tanwee Alkutkar, Juliana Bortolatto, Tiago B R Castro, Will Dumm, Chris Jennings-Shaffer, Tongqiu Jia and 11 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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

William S DeWittDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Ashni A VoraLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Tatsuya ArakiLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Jared G GallowayComputational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Tanwee AlkutkarDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Juliana BortolattoLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Tiago B R CastroLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Will DummComputational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Chris Jennings-ShafferComputational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Tongqiu JiaComputational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Luka MesinLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Juhee PaeLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.
Duncan K RalphComputational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Jesse D BloomDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0003-1267-3408
Armita NourmohammadComputational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Yun S SongDepartment of Statistics, University of California, Berkeley, CA, USA.ORCID 0000-0002-0734-9868
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0001-7153-3769
Tyler N StarrDepartment of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.ORCID 0000-0001-6713-6904
Frederick A MatsenDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID 0000-0003-0607-6025
Gabriel D VictoraLaboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA.ORCID 0000-0001-8807-348X

Funding

Dynamics of Antigen-Driven Selection in Germinal CentersR01AI119006 · NIAID · ROCKEFELLER UNIVERSITY · PI Gabriel D Victora · 2017 to 2026
$5.7M
Molecular control of germinal center selection and affinity maturationR01AI139117 · NIAID · ROCKEFELLER UNIVERSITY · PI Gabriel D Victora · 2018 to 2026
$3.9M
Blending deep learning with probabilistic mechanistic models to predict and understand the evolution and function of adaptive immune receptorsR01AI146028 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MATSEN, FREDERICK ALBERT · 2019 to 2024
$3.4M
Inferring the rules of antibody evolution using replicated germinal centersR01AI180451 · NIAID · ROCKEFELLER UNIVERSITY · PI Gabriel D Victora · 2024 to 2026
$2.4M
High-Performance Compute Cluster for Comprehensive Cancer and Infectious Diseases ResearchS10OD028685 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, PHILIP · 2020 to 2020
$2.0M
The evolutionary landscape of HIV broadly neutralizing antibody developmentDP2AI177890 · NIAID · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Tyler Nelson Starr · 2023 to 2026
$1.8M
Learning a molecular shape space for the adaptive immune systemR35GM142795 · NIGMS · UNIVERSITY OF WASHINGTON · PI NOURMOHAMMAD, ARMITA · 2021 to 2025
$1.8M
Scalable Computational Methods for Genealogical Inference: from species level to single cellsR01HG013117 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Ian H Holmes, RASMUS NIELSEN · 2024 to 2026
$1.7M
NHGRI NIH HHS R01 HG013117NIAID NIH HHS DP2 AI177890NIAID NIH HHS R01 AI119006NIAID NIH HHS R01 AI139117NIAID NIH HHS R01 AI146028NIAID NIH HHS R01 AI180451NIGMS NIH HHS R35 GM142795NIH HHS S10 OD028685
6 · The paper itself

Abstract

Darwinian evolution of immunoglobulin genes within germinal centers (GC) underlies the progressive increase in antibody affinity following antigen exposure. Whereas the mechanics of how competition between GC B cells drives increased affinity are well established, the dynamical evolutionary features of this process remain poorly characterized. We devised an experimental evolution model in which we "replay" over one hundred instances of a clonally homogenous GC reaction and follow the selective process by assigning affinities to all cells using deep mutational scanning. Our data reveal how GCs achieve predictable evolutionary outcomes through the cumulative effects of many rounds of imperfect selection, acting on a landscape shaped heavily by somatic hypermutation (SHM) targeting biases. Using time-calibrated models, we show that apparent features of GC evolution such as permissiveness to low-affinity lineages and early plateauing of affinity are best explained by survivorship biases that distort our view of how affinity progresses over time.

Identifiers

PMID40661619
PMCPMC12258878

What OpenQuestion holds

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Registered trials

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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.