AUTHOR=Meng Danyang , Wang Jinhao , Du Lianqun , Hu Xiaojun , Liu Ying , Zhang Pengcheng , Wang Jianjie , Dong Qingyang 

TITLE=PD-L1 in plasmacytoid dendritic cells promote HBV persistence through disrupting humoral immune response

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1545667

DOI=10.3389/fimmu.2025.1545667

ISSN=1664-3224

ABSTRACT=ObjectiveTo investigate the efficacy of PD-L1 blockade in restoring humoral immune response against HBV.MethodsHBV‐persistent C57BL/6J mice were established through hydrodynamic tail vein injection of 10 µg pAAV‐HBV1.2 plasmid. Subsequently, mice treated i.p. with anti‐PD‐L1 and/or anti‐CTLA‐4 at specified time points, with dosages of 500 µg, 250 µg, and 250 µg, respectively. Additionally, 5 × 105 magnetic bead‐purified 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.ResultsPD-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.ConclusionpDCs 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.