{
  "abstract": "Activation-induced cytidine deaminase (AID), encoded by AICDA, facilitates class-switch recombination (CSR) and somatic hypermutation (SHM) in activated B cells. Loss of AID function causes hyper-IgM syndrome type 2 (HIGM2). While typically autosomal recessive, three C-terminal truncation variants have been reported to act in autosomal dominant manner. We describe a novel heterozygous AICDA nonsense variant, c.589G>T (p.G197*), that truncates the final two C-terminal residues of AID and results in adult-onset HIGM2. Single-cell sequencing of primary patient B cells revealed a complete block in CSR and a [~]10-fold reduction in SHM. AICDA mRNA expression was balanced between wild-type and variant alleles, yet AID protein abundance was reduced to [~]56% with normal subcellular localization. Remarkably, inducible germinal center (iGB) cultures restored CSR in purified naive patient B cells. CRISPR-Cas9 editing of healthy donor B cells confirmed that the iGB platform can rescue B cells harboring heterozygous, but not homozygous, AICDA variants. These results demonstrate that even a two-amino-acid truncation at the AID C-terminus is sufficient to disrupt its function and cause HIGM2.",
  "abstract_shown": true,
  "affiliations": [
    "Aarhus University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "K. Green"
    },
    {
      "name": "A. B. Rovsing"
    },
    {
      "name": "E. Terczynska-Dyla"
    },
    {
      "name": "L. Jensen"
    },
    {
      "name": "K. Machalica"
    },
    {
      "name": "J. H. Wolff"
    },
    {
      "name": "L. Westerberg"
    },
    {
      "name": "C. S. Larsen"
    },
    {
      "name": "L. Lin"
    },
    {
      "name": "J. G. Mikkelsen"
    },
    {
      "name": "J. M. B. Jensen"
    },
    {
      "affs": [
        0
      ],
      "name": "S. E. Degn"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b2phhyn2vk1nk.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762264",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762264v1.full",
  "id": "b2phhyn2vk1nk",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762264v1",
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762264v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b2phhyn2vk1nk.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T00:20:41Z",
      "native_id": "10.64898/2026.10.27.762264",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762264v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "A minimal two-residue C-terminal truncation of AID in adult-onset hyper-IgM syndrome type 2 (HIGM2)",
  "title_text": "A minimal two-residue C-terminal truncation of AID in adult-onset hyper-IgM syndrome type 2 (HIGM2)",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:11Z",
  "url": "https://research.draconitic.com/paper/b2phhyn2vk1nk",
  "venue": "bioRxiv",
  "versions": []
}