Evidence map›Paper›PMID 42013839›Full record

ArticleCell systems2026

Phased fragility and stability of non-genetic B cell states in the germinal center accelerate the genetic evolution of antibodies.

Mark Y Xiang, Haripriya Vaidehi Narayanan, Vaibhava Kesarwani, Rohan Vanheusden, Tiffany Wang, Alexander Hoffmann

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2026. 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

5 · Who and what money

Authors and funding

6 authors.

Mark Y XiangInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Bioinformatics Program, University of California, Los Angeles, Los Angeles, CA, USA.
Haripriya Vaidehi NarayananInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Vaibhava KesarwaniInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
Rohan VanheusdenInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA; Systems Biology Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tiffany WangInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
Alexander HoffmannInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: ahoffmann@ucla.edu.

Funding

Characterizing functional states of macrophages via their stimulus-responsesR01AI173214 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Alexander Hoffmann · 2023 to 2026
$2.8M
Cell decision underlying B-cell immune responsesR01AI132731 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER · 2018 to 2022
$2.2M
The NFkB System in Dendritic CellsR01AI127867 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER · 2018 to 2022
$2.2M
NIAID NIH HHS R01 AI127867NIAID NIH HHS R01 AI132731NIAID NIH HHS R01 AI173214
6 · The paper itself

Abstract

Vaccine responses depend on the Darwinian genetic evolution of B cells to generate high-affinity antibodies. However, B cells gain non-genetic heterogeneity while searching for antigen and T helper cells, but then their non-genetic cell states remain stable within proliferative clonal bursts. We explored the functional consequence of this dynamic control of non-genetic variability by developing a mathematical model, integrating a wealth of immunological knowledge. We discovered that variability in B cell fate decisions does not impair but instead accelerates affinity maturation by allowing high-affinity outliers to escape plasma cell differentiation and seed further rounds of Darwinian evolution. During clonal bursts, non-genetic cell state stability further promotes their amplification. The resulting model correctly predicts emergent vaccine response properties in mouse strains with altered B cell fate decision profiles. Our work reconciles classical B cell clonal selection theory with the experimentally observed non-genetic variability, and it provides an interpretable knowledge-based modeling framework to support personalized vaccination strategies.

Indexed as

AntibodiesB-LymphocytesGerminal CenterAnimalsCell DifferentiationEvolution, MolecularMiceAntibodiesaffinity maturationcell fate stochasticitycell-to-cell heterogeneityDarwinian evolutionepigenetic heritabilitygerminal center reactionknowledge-based modelnon-genetic cell stateprobabilistic cell fate mapvaccine response

Identifiers

PMID42013839
PMCPMC13179148

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.