{
  "abstract": "The transcription factors IRF4 and BLIMP1 (PRDM1) promote plasma cell (PC) differentiation by repressing B cell identity genes while inducing the unfolded protein response, ER/Golgi biogenesis, and immunoglobulin secretion. How IRF4 and BLIMP1 partition and coordinate their genomic activities during plasma cell differentiation remains unresolved. Using naive human B cells and a stepwise in vitro differentiation system, we performed CRISPR/Cas9 perturbations of IRF4 or PRDM1 in plasma cell precursors followed by single-cell RNA sequencing. Despite their mutually reinforced expression and shared recognition of related IRF-family motifs (ISREs and EICEs), loss of IRF4, but not of BLIMP1, yielded a stunted intermediate with incomplete silencing of B cell identity genes and defective induction of the secretory program. Multiome profiling, base-pair-resolution motif modeling, CUT&RUN, and DNA-binding assays identified non-conserved nucleotides within ISRE/EICE motifs that discriminate IRF4 from BLIMP1 binding. These findings define an ISRE/EICE motif lexicon that predicts differential IRF4 and BLIMP1 occupancy and are consistent with a temporally ordered model, in which IRF4 first acts independently and then in concert with BLIMP1 to promote PC differentiation.",
  "abstract_shown": true,
  "affiliations": [
    "University of Pittsburgh"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "L. C. Lau"
    },
    {
      "name": "S. Lal"
    },
    {
      "name": "J. Fan"
    },
    {
      "name": "N. Pease"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Singh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/616srtrnwdh08.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.06.15.732353",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.15.732353v2.full",
  "id": "616srtrnwdh08",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.15.732353v2",
  "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/10.64898/2026.06.15.732353v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/616srtrnwdh08.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:08Z",
      "native_id": "10.64898/2026.06.15.732353",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.15.732353v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Sequential and coordinated control of human plasma cell differentiation by IRF4 and BLIMP1 associated with a discriminating ISRE/EICE motif lexicon",
  "title_text": "Sequential and coordinated control of human plasma cell differentiation by IRF4 and BLIMP1 associated with a discriminating ISRE/EICE motif lexicon",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:08Z",
  "url": "https://research.draconitic.com/paper/616srtrnwdh08",
  "venue": "bioRxiv",
  "versions": []
}