{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:01:54Z","timestamp":1785132114029,"version":"3.55.0"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Double-negative (DN) B cells have emerged as pivotal players in autoimmune diseases, transitioning from an overlooked exhausted subpopulation to a lineage with potent pathogenic potential. Based on surface marker expression, DN B cells are subdivided into four distinct subsets: DN1, DN2, DN3, and DN4. This review provides a comprehensive overview of these subsets, focusing on their origins, phenotypes, and developmental trajectories. In disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sj\u00f6gren\n                    <jats:bold>\u2019<\/jats:bold>\n                    s syndrome (pSS), and multiple sclerosis (MS), expanded DN B cells infiltrate target organs via chemokine receptor-mediated pathways and interact with T cells to drive the pathological remodeling of the local immune microenvironment. Elucidating the regulatory mechanisms of DN B cell differentiation and their functional heterogeneity across disease contexts will provide a critical foundation for the development of targeted precision immunotherapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1839432","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:41:20Z","timestamp":1785130880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The pathogenic role of double-negative B cells in autoimmune diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanzuo","family":"Wu","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Yang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongsheng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqun","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41392-024-01952-8","article-title":"Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders","volume":"9","author":"Song","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2022.102266","article-title":"The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention","volume":"80","author":"Miller","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1626082","article-title":"Autoimmune disease: genetic susceptibility, environmental triggers, and immune dysregulation. 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