{
  "abstract": "B cell activating factor (BAFF), originally characterized as a canonical survival factor for B cells, is now recognized as a pleiotropic immunoregulator that bridges innate and adaptive immunity. Its biological effects are highly context-dependent, manifesting as promotion of malignant B-cell survival in hematological malignancies, conflicting activities in solid tumors, and disruption of B-cell tolerance in autoimmune diseases. Current literature has largely examined BAFF within disease-specific frameworks, leaving cross-disease mechanistic relationships inadequately resolved. In this review, we propose a multi-factorial framework for integrating evidence across cancer and autoimmunity through four proposed variables: ligand concentration, oligomeric form, cellular source, and receptor availability. By dissecting receptor signaling via BAFF receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA), we evaluate the therapeutic landscape, safety profiles, and combination strategies of BAFF-targeted agents. The framework is a working hypothesis, not a validated causal model. We propose three integrated perspectives: (i) a proposed multi-factorial framework for interpreting BAFF’s divergent functions; (ii) a conceptual, testable inverted U-shaped working hypothesis for solid tumors, without validated concentration thresholds; and (iii) the translational utility of BAFF system molecules as stratification biomarkers and precision therapeutic targets. Autoimmune disease data provide conceptual support for this concentration-form-context framework, which was initially developed to reconcile contradictory observations in tumors. The framework requires direct experimental titration and oligomer-specific validation. Finally, we identify critical knowledge gaps, including distinct signaling pathways elicited by BAFF oligomers and crosstalk with inflammatory networks, to inform next-generation personalized immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "The First Affiliated Hospital of Dalian Medical University",
    "Dalian Medical University",
    "Department of Urology, First Hospital of Shanxi Medical University",
    "Department of Gastroenterology, Shengjing Hospital of China Medical University",
    "Department of Cardiology, Dandong First Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiayi Shang"
    },
    {
      "affs": [
        1
      ],
      "name": "Minli Jin"
    },
    {
      "affs": [
        2
      ],
      "name": "Kui Jiang"
    },
    {
      "affs": [
        3
      ],
      "name": "Weiqi Liu"
    },
    {
      "affs": [
        4
      ],
      "name": "Jinji Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaochi Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ctbfd9esktfme.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1975879",
  "fulltext_url": null,
  "id": "ctbfd9esktfme",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1975879/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7224104208",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ctbfd9esktfme.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1975879",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1975879/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Context-dependent immunoregulation by BAFF: reconciling its pro-tumorigenic, anti-tumor, and autoimmune roles through a multi-factorial lens",
  "title_text": "Context-dependent immunoregulation by BAFF: reconciling its pro-tumorigenic, anti-tumor, and autoimmune roles through a multi-factorial lens",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/ctbfd9esktfme",
  "venue": "Frontiers in Immunology",
  "versions": []
}