ArticleCell2026
Replaying germinal center evolution on a quantified affinity landscape.
Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Germinal Center Selection and Plasma Cell Differentiation.Immunological reviews · 2026Review
- Clonal dynamics of germinal center refueling by secondary immunization.bioRxiv : the preprint server for biology · 2026Article
- Entrenchment of germline amino-acid differences in antibody affinity maturation.bioRxiv : the preprint server for biology · 2026Article
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- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
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- Paraplume: A fast and accurate antibody paratope prediction method provides insights into repertoire-scale binding dynamics.PLoS computational biology · 2026Article
- The multilayered identity of B cell memory.Cellular & molecular immunology · 2026Review
- The current landscape of adaptive immune receptor genomic and repertoire data: OGRDB and VDJbase.Nucleic acids research · 2026Article
- Article
- Nucleotide context models outperform protein language models for predicting antibody affinity maturation.bioRxiv : the preprint server for biology · 2025Article
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- Antibody-mediated feedback modulates interclonal competition in the germinal center.bioRxiv : the preprint server for biology · 2025Article
- Vulnerability in the breadth evolution of an influenza broadly neutralizing antibody.bioRxiv : the preprint server for biology · 2025Article
- Dynamics of local B cell migration during affinity maturation in the human tonsil.bioRxiv : the preprint server for biology · 2025Article
- Separating selection from mutation in antibody language models.bioRxiv : the preprint server for biology · 2025Article
- TyCHE enables time-resolved lineage tracing of heterogeneously-evolving populations.bioRxiv : the preprint server for biology · 2025Article
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21 authors.
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Abstract
Darwinian evolution of immunoglobulin genes within germinal centers (GCs) underlies the progressive increase in antibody affinity following antigen exposure. Whereas the cellular mechanics of how competition between B cells increases affinity are well established, the evolutionary dynamics of this process are less clear. We developed an experimental evolution model in which we "replay" over one hundred monoclonal GC reactions, assigning affinities to each cell using deep mutational scanning. Our data reveal how GCs achieve predictable outcomes by means of noisy but persistent selection on an affinity landscape whose exploration is heavily constrained by somatic hypermutation biases. We infer a fitness landscape that quantitatively recapitulates the affinity maturation trajectory of our clone and find that apparent features of GC selection, such as permissiveness to low-affinity lineages and rapid plateauing of affinity, are likely artifacts of survivorship biases that distort our view of how B cell affinity progresses over time.
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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.