{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genome Sciences, University of Washington, Seattle, WA, USA; Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA",
    "Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA",
    "Department of Genome Sciences, University of Washington, Seattle, WA, USA",
    "Laboratory of Lymphocyte Dynamics, the Rockefeller University, New York, NY, USA",
    "BioMedicine Design, Pfizer, Cambridge, MA, USA",
    "Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA",
    "Laboratory of Lymphocyte Dynamics, the Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, New York, NY, USA",
    "Howard Hughes Medical Institute, New York, NY, USA",
    "Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA",
    "Department of Genome Sciences, University of Washington, Seattle, WA, USA; Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA, USA",
    "Howard Hughes Medical Institute, Seattle, WA, USA",
    "Department of Applied Mathematics, University of Washington, Seattle, WA, USA",
    "Department of Physics, University of Washington, Seattle, WA, USA",
    "Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, USA",
    "Department of Statistics and Computer Science Division, University of California, Berkeley, Berkeley, CA, USA",
    "Department of Statistics, University of California, Berkeley, CA, USA",
    "Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA",
    "Department of Genome Sciences, University of Washington, Seattle, WA, USA; Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA, USA; Department of Statistics, University of Washington, Seattle, WA, USA. Electronic address: matsen@fredhutch.org",
    "Laboratory of Lymphocyte Dynamics, the Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, New York, NY, USA. Electronic address: victora@rockefeller.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "William S. DeWitt",
      "orcid": "0000-0002-6802-9139"
    },
    {
      "affs": [
        3
      ],
      "name": "Ashni A. Vora"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Tatsuya Araki",
      "orcid": "0000-0002-6203-7250"
    },
    {
      "affs": [
        1
      ],
      "name": "Jared Galloway",
      "orcid": "0000-0001-5838-7840"
    },
    {
      "affs": [
        5
      ],
      "name": "Tanwee Alkutkar",
      "orcid": "0000-0002-7530-7424"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Juliana Bortolatto",
      "orcid": "0000-0001-8779-5464"
    },
    {
      "affs": [
        3
      ],
      "name": "Tiago B. R. Castro",
      "orcid": "0000-0002-0359-0611"
    },
    {
      "affs": [
        1
      ],
      "name": "Will Dumm",
      "orcid": "0000-0002-8617-476X"
    },
    {
      "affs": [
        1
      ],
      "name": "Chris Jennings-Shaffer",
      "orcid": "0000-0002-6492-3854"
    },
    {
      "affs": [
        1
      ],
      "name": "Tongqiu Jia",
      "orcid": "0000-0002-6012-6436"
    },
    {
      "affs": [
        3
      ],
      "name": "Luka Mesin",
      "orcid": "0000-0001-9852-6841"
    },
    {
      "affs": [
        5
      ],
      "name": "Gabriel Ozorowski",
      "orcid": "0000-0002-9695-8138"
    },
    {
      "affs": [
        3
      ],
      "name": "Juhee Pae",
      "orcid": "0000-0003-0676-0935"
    },
    {
      "affs": [
        1
      ],
      "name": "Duncan Ralph",
      "orcid": "0000-0002-2527-8610"
    },
    {
      "affs": [
        9,
        1,
        2,
        10
      ],
      "name": "Jesse D. Bloom",
      "orcid": "0000-0003-1267-3408"
    },
    {
      "affs": [
        1,
        11,
        12,
        13
      ],
      "name": "Armita Nourmohammad",
      "orcid": "0000-0002-6245-3553"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Yun S. Song",
      "orcid": "0000-0002-0734-9868"
    },
    {
      "affs": [
        5
      ],
      "name": "Andrew B. Ward"
    },
    {
      "affs": [
        16
      ],
      "name": "Tyler N. Starr",
      "orcid": "0000-0001-6713-6904"
    },
    {
      "affs": [
        17,
        1,
        2,
        10
      ],
      "name": "Frederick A. Matsen IV",
      "orcid": "0000-0003-0607-6025"
    },
    {
      "affs": [
        18,
        7,
        8
      ],
      "name": "Gabriel D. Victora",
      "orcid": "0000-0001-8807-348X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5kznfcd13q77k.bib",
  "cited_by": 31,
  "doi": "10.1016/j.cell.2026.05.013",
  "fulltext_url": null,
  "id": "5kznfcd13q77k",
  "issns": [
    "0092-8674",
    "1097-4172"
  ],
  "landing_url": "https://doi.org/10.1016/j.cell.2026.05.013",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Evolution and Genetic Dynamics"
    ]
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  "openalex": "W4411060598",
  "pdf_url": null,
  "pmcid": "PMC12258878",
  "pmid": "40661619",
  "published": "2026-06-05",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/5kznfcd13q77k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W4411060598",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.cell.2026.05.013"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Evolution and Genetic Dynamics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Replaying germinal center evolution on a quantified affinity landscape",
  "title_text": "Replaying germinal center evolution on a quantified affinity landscape",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T13:20:47Z",
  "url": "https://research.draconitic.com/paper/5kznfcd13q77k",
  "venue": "Cell",
  "versions": []
}