{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:30:27Z","timestamp":1790371827775,"version":"4.1.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"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:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the efficacy of PD-L1 blockade in restoring humoral immune response against HBV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HBV\u2010persistent C57BL\/6J mice were established through hydrodynamic tail vein injection of 10 \u00b5g pAAV\u2010HBV1.2 plasmid. Subsequently, mice treated i.p. with anti\u2010PD\u2010L1 and\/or anti\u2010CTLA\u20104 at specified time points, with dosages of 500 \u00b5g, 250 \u00b5g, and 250 \u00b5g, respectively. Additionally, 5 \u00d7 10<jats:sup>5<\/jats:sup> magnetic bead\u2010purified plasmacytoid dendritic cells (pDCs) were adoptively transferred i.v. into the acute mouse model followed by anti-PD-L1 treatment. Quantitative real-time PCR was employed to assess the expression levels of costimulatory and tolerogenic molecules in two dendritic cell subsets. Serum HBsAg and HBsAb were measured using ELISA. Flow cytometry was utilized to quantify T follicular helper (Tfh) cells, regulatory T cells (Treg), and germinal center (GC) B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD-L1 blockade markedly enhanced the differentiation of Tfh cells and GC B cells in HBV-persistent C57BL\/6J mice, thereby promoting HBV clearance. Additionally, pDCs exhibited an increased capacity to induce immune tolerance, with pDCs isolated from HBV carriers inducing viral persistence. This persistence was effectively counteracted by treatment with anti-PD-L1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>pDCs mediate the dysregulation of the humoral immune response to HBV through PD-L1 in chronic hepatitis B infection, highlighting a promising target for the management of chronic HBV.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1545667","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:31:09Z","timestamp":1745472669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["PD-L1 in plasmacytoid dendritic cells promote HBV persistence through disrupting humoral immune 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