{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T08:01:44Z","timestamp":1775894504055,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,8]]},"group-title":"Immunology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in IRF7 uncovered the IRF7 role in regulating autoimmune germinal center (GC), plasma cell (PC) and autoantibody responses and disease. IRF7, however, was dispensable for foreign antigen driven GC, PC and antibody responses. Competitive bone marrow (BM) chimeras highlighted the importance of IRF7 in hematopoietic cells in spontaneous GC and PC differentiation. Single-cell-RNAseq of SLE-prone B cells indicated IRF7 mediated B cell differentiation through GC and PC fates. Mechanistic studies revealed that IRF7 promoted B cell differentiation through GC and PC fates by regulating the transcriptome, translation, and metabolism of SLE-prone B cells. Mixed BM chimeras demonstrated a requirement for B cell-intrinsic IRF7 in IgG autoantibody production but not sufficient for promoting spontaneous GC and PC responses. Altogether, we delineate previously unknown B cell-intrinsic and -extrinsic mechanisms of IRF7-promoted spontaneous GC and PC responses, loss of tolerance, autoantibody production and SLE development.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>Fike et al. describe previously unknown mechanisms by which IRF7 controls autoimmune B cell and autoantibody responses. Mechanistic studies guided by single-cell-RNAseq and ChIPseq reveal that IRF7 promotes B cell differentiation through germinal center and plasma cell fates by regulating the transcriptome, translation, and metabolism of lupus-prone B cells.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.04.636277","type":"posted-content","created":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T17:00:20Z","timestamp":1739034020000},"source":"Crossref","is-referenced-by-count":0,"title":["IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints"],"prefix":"10.64898","author":[{"given":"Adam J.","family":"Fike","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen N.","family":"Bricker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, 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17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia L.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara A.","family":"Luckenbill","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renan","family":"Sauteraud","sequence":"additional","affiliation":[{"name":"Public Health Science, Pennsylvania State University College of 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