{
  "abstract": "Autoreactive B cells must escape immune tolerance mechanisms to drive autoimmune disease, potentially through alternative paths to memory and antibody-secreting cell formation. \"Atypical\" B cells represent one such alternative pathway and are expanded in several human autoimmune diseases. Atypical B cells display phenotypic heterogeneity, but how this connects with differences in transcriptional programming, isotype switching and somatic hypermutation is incompletely understood in type 1 diabetes (T1D). Screening efforts to detect T1D prior to clinical diabetes onset affords an opportunity to study B cells early in immunopathogenesis, in which they primarily function as antigen-presenting cells. Prior evidence points to atypical B cell populations as reservoirs for islet autoreactivity in human T1D. We therefore developed sorting strategies to enrich for atypical and other autoreactive-prone B cell populations from the peripheral blood of early-stage T1D individuals and performed single-cell RNA/BCR-sequencing. We identified four transcriptionally defined atypical B cell clusters, each showing differential upregulation of atypical B cell defining genes. Additional gene expression changes were noted in broadly transcriptionally similar, but phenotypically distinct atypical B cell populations, with differences noted in the average extent of isotype switching and somatic hypermutation. Some atypical B cell populations showed extensive clonal sharing with classical memory or plasmablast subsets, consistent with relationships amongst these subsets. B cells reactive against a key islet autoantigen, insulin, were enriched in select atypical B cell populations. These findings highlight specific atypical B cell populations and features with potential value as biomarkers of disease progression or response to immunotherapy in T1D, and potentially other autoimmune diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Vanderbilt Health"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "L. E. Bass"
    },
    {
      "name": "L. M. Clark"
    },
    {
      "name": "B. Han"
    },
    {
      "name": "D. J. Moore"
    },
    {
      "affs": [
        0
      ],
      "name": "R. H. Bonami"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e2n46bbdmfhhz.bib",
  "cited_by": 1,
  "doi": "10.64898/2026.09.30.754202",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.754202v1.full",
  "id": "e2n46bbdmfhhz",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.754202v1",
  "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",
      "1311|Diabetes and associated disorders"
    ]
  ],
  "openalex": "W7218494886",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.754202v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e2n46bbdmfhhz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:52Z",
      "native_id": "10.64898/2026.09.30.754202",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.754202v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Transcriptionally distinct atypical B cell populations contribute to insulin autoreactivity and show differential activation, isotype switching, and somatic hypermutation in early-stage type 1 diabetes individuals",
  "title_text": "Transcriptionally distinct atypical B cell populations contribute to insulin autoreactivity and show differential activation, isotype switching, and somatic hypermutation in early-stage type 1 diabetes individuals",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:52Z",
  "url": "https://research.draconitic.com/paper/e2n46bbdmfhhz",
  "venue": "bioRxiv",
  "versions": []
}