{
  "abstract": "Diacylglycerol (DAG) is a critical second messenger downstream of the B-cell receptor (BCR), but how DAG signaling is regulated during B-cell development and humoral responses remains incompletely understood. Here, complementary gain- and loss-of-function approaches revealed stage-specific requirements for diacylglycerol kinase (DGK)-regulated signaling in B cells. Expression of the gain-of-function DGK{zeta} mutant DGK{zeta}{Delta}NLS had limited effects on early BM B-cell development but progressively impaired transitional and mature B-cell populations. DGK{zeta}{Delta}NLS attenuated BCR-induced ERK1/2 and mTOR signaling, activation, and proliferation and, when expressed in AID-expressing B cells, reduced GC B-cell survival and T-dependent IgG responses without detectably impairing GC B-cell proliferation in vivo. Conversely, combined DGK/{zeta} deficiency resulted in marked spontaneous GC B-cell expansion associated with enhanced ERK1/2, Akt, and S6 signaling and increased glucose uptake. Despite this steady-state GC expansion, DGK/{zeta}-deficient mice developed spontaneous autoreactivity and mounted impaired antigen-specific antibody responses. Thus, B-cell developmental stages exhibit differential sensitivity to altered DGK activity, and opposing perturbations of DGK-regulated signaling produce reciprocal effects on GC B-cell accumulation while both compromise productive humoral immunity. These findings identify DGKs as critical regulators that tune lipid signaling for B-cell maturation, GC homeostasis, and effective antibody responses.",
  "abstract_shown": true,
  "affiliations": [
    "Duke University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "J. Xie"
    },
    {
      "name": "S. Zhang"
    },
    {
      "name": "W. Lee"
    },
    {
      "name": "H. Tao"
    },
    {
      "name": "Y. Pan"
    },
    {
      "name": "X. Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "X.-P. Zhong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8rmfk30hryc1b.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.05.756823",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756823v1.full",
  "id": "8rmfk30hryc1b",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756823v1",
  "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",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7221686645",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756823v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8rmfk30hryc1b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:26Z",
      "native_id": "10.64898/2026.10.05.756823",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756823v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Diacylglycerol Kinases Balance DAG Signaling to Control B Cell Maturation, Germinal Center Homeostasis, and Humoral Immunity",
  "title_text": "Diacylglycerol Kinases Balance DAG Signaling to Control B Cell Maturation, Germinal Center Homeostasis, and Humoral Immunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:26Z",
  "url": "https://research.draconitic.com/paper/8rmfk30hryc1b",
  "venue": "bioRxiv",
  "versions": []
}