{
  "abstract": "Germinal center (GC) B-cells give rise to the majority of non-Hodgkin lymphomas, underscoring the need to pinpoint critical processes that initiate and drive lymphomagenesis. Lymphoma driver mutations can alter GC B cell functions and B cell fate decisions. Here, we studied how EZH2 oncogenic mutation in GC B cells alters cellular motility and interactions with T follicular helper (Tfh) cells and follicular dendritic cells (FDCs) to determine B cell fate. By combining intravital imaging, single-cell behavior analyses, and RNA sequencing, we uncover how lymphoma-associated EZH2 mutations reprogram the behaviors of GC B cells in vivo. We found that EZH2 mutations increased single-cell motility speeds and morphological plasticity of GC B cells, redirecting migration toward the FDC-rich light zone subregions rather than to the dark zone. Although mutant EZH2 GC B cells exhibited normal engagement quality with FDCs, they showed shorter interaction times and reduced surface engagement with Tfh cells. Notably, EZH2 mutant B cells required prior contact with FDC before engaging with Tfh cells, thus impairing DZ recycling. This motility phenotype scaled with local mutant clone abundance, suggesting a behavioral strategy underlying how mutant cells outcompete WT cells. Lastly, we developed scMOTIPh, a computational framework that integrates single-cell behavioral features with transcriptomic profiles. Applying scMOTIPh to mutant GC B cells within the FDC-rich zone revealed enhanced ATP production, metabolic and antigen-presentation programs, and suppression of cell-death pathways, which is consistent with a tendency for malignant transformation and survival fitness. These findings provide an in vivo, single-cell view of how an epigenetic lesion rewires the local microenvironment by modulating single-cell behaviors within native GCs, revealing a dynamic mechanism for early lymphomagenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Johns Hopkins University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "C. Min"
    },
    {
      "name": "K. Choe"
    },
    {
      "name": "X. Chen"
    },
    {
      "name": "I. Karagiannidis"
    },
    {
      "name": "N. Sivakumar"
    },
    {
      "name": "C. Xu"
    },
    {
      "name": "A. Melnick"
    },
    {
      "affs": [
        0
      ],
      "name": "J. M. Phillip"
    },
    {
      "name": "W. Beguelin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fvm4p1kdhqv26.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.02.748910",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748910v1.full",
  "id": "fvm4p1kdhqv26",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748910v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2734|Lymphoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7210280031",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748910v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fvm4p1kdhqv26.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:45Z",
      "native_id": "10.64898/2026.09.02.748910",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.02.748910v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Intravital single-cell behavior profiling reveals disrupted germinal center B cell motility and interactions by EZH2 gain-of-function mutation",
  "title_text": "Intravital single-cell behavior profiling reveals disrupted germinal center B cell motility and interactions by EZH2 gain-of-function mutation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:50Z",
  "url": "https://research.draconitic.com/paper/fvm4p1kdhqv26",
  "venue": "bioRxiv",
  "versions": []
}