{
  "abstract": "Borrelia burgdorferi, the causative agent of Lyme borreliosis, persists in mammalian hosts despite robust activation of innate and adaptive immunity. A hallmark of murine infection is the production of low-avidity antibodies, yet the immunological mechanisms underlying this defective humoral response remain poorly understood. Here, we used single-cell RNA sequencing of draining lymph node cells from Borrelia-infected mice at days 7 and 14 post-infection, comparing transcriptional profiles with those from mice immunised with heat-killed Borrelia or with a potent germinal centre-inducing protein immunisation. Borrelia infection induced a rapid germinal centre response, however, light zone B cells displayed diminished expression of co-stimulatory and T-B cell interaction molecules while maintaining core germinal centre identity markers, suggesting impaired positive selection. T follicular helper cells upregulated multiple inhibitory checkpoint receptor genes, most prominently Ctla4, alongside an active germinal centre engagement programme. Foxp3? regulatory T cells upregulated genes associated with follicular-homing and suppressive function, including those implicated in CTLA-4-mediated trans-endocytosis. To test whether inhibitory signalling contributes to the impaired humoral response, infected mice were treated with anti-CTLA-4 blocking antibody. CTLA-4 blockade significantly increased plasma cell numbers and enhanced both the magnitude and avidity of Borrelia-specific IgG responses, including the induction of complement-fixing IgG2a. These findings reveal that CTLA-4-dependent inhibitory signalling contributes to defective antibody quality during Borrelia infection, identifying a mechanism by which dysregulated T cell responses may facilitate impaired humoral control of a persistent spirochaetal pathogen.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "V. J. Mäkinen"
    },
    {
      "name": "J. Alinikula"
    },
    {
      "name": "R. Fair-Mäkelä"
    },
    {
      "name": "P. Sundqvist"
    },
    {
      "name": "M. Salmi"
    },
    {
      "name": "P. Mattila"
    },
    {
      "name": "A. Pietikäinen"
    },
    {
      "name": "J. Hytönen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7ss9sjvgkseky.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.30.763258",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763258v1.full",
  "id": "7ss9sjvgkseky",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763258v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763258v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7ss9sjvgkseky.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T00:21:40Z",
      "native_id": "10.64898/2026.10.30.763258",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763258v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "CTLA-4 checkpoint signalling modulates germinal centre dynamics and antibody avidity during Borrelia burgdorferi infection in mice.",
  "title_text": "CTLA-4 checkpoint signalling modulates germinal centre dynamics and antibody avidity during Borrelia burgdorferi infection in mice.",
  "type": "preprint",
  "updated_at": "2026-11-05T00:21:09Z",
  "url": "https://research.draconitic.com/paper/7ss9sjvgkseky",
  "venue": "bioRxiv",
  "versions": []
}