{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:06:49Z","timestamp":1769472409975,"version":"3.49.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270631"],"award-info":[{"award-number":["82270631"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Center of Shandong University","award":["2021SDUCRCB006"],"award-info":[{"award-number":["2021SDUCRCB006"]}]},{"name":"Young Taishan Scholars","award":["tsqn202103169"],"award-info":[{"award-number":["tsqn202103169"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"DOI":"10.1186\/s12985-025-03055-4","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T03:46:48Z","timestamp":1766202408000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral and intrahepatic B-cell subsets contribute to HBeAg seroconversion in patients with chronic hepatitis B"],"prefix":"10.1186","volume":"23","author":[{"given":"Jing","family":"Zuo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Qi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Ming","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng-Jie","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Xin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Ru","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"issue":"10042","key":"3055_CR1","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/S0140-6736(16)31144-8","volume":"388","author":"THE L","year":"2016","unstructured":"THE L. Towards elimination of viral hepatitis by 2030 [J]. Lancet. 2016;388(10042):308.","journal-title":"Lancet"},{"issue":"3","key":"3055_CR2","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.jhep.2019.11.003","volume":"72","author":"M Cornberg","year":"2020","unstructured":"Cornberg M, Lok AS, Terrault NA, et al. Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV treatment endpoints conference(\u2021). J Hepatol. 2020;72(3):539\u201357.","journal-title":"J Hepatol"},{"issue":"8","key":"3055_CR3","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1084\/jem.191.8.1269","volume":"191","author":"MK Maini","year":"2000","unstructured":"Maini MK, Boni C, Lee CK, et al. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med. 2000;191(8):1269\u201380.","journal-title":"J Exp Med"},{"key":"3055_CR4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.coviro.2021.04.003","volume":"49","author":"C CHIALE","year":"2021","unstructured":"CHIALE C, MARCHESE A M, ROBEK MD. Innate immunity and HBV persistence [J]. Curr Opin Virol. 2021;49:13\u201320.","journal-title":"Curr Opin Virol"},{"issue":"7","key":"3055_CR5","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1093\/infdis\/jix683","volume":"217","author":"H Liu","year":"2018","unstructured":"Liu H, Li F, Zhang X, et al. Differentially expressed intrahepatic genes contribute to control of hepatitis B virus replication in the inactive carrier phase. J Infect Dis. 2018;217(7):1044\u201354.","journal-title":"J Infect Dis"},{"issue":"2","key":"3055_CR6","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.jhep.2022.02.016","volume":"77","author":"MONTANARINR RAM\u00edREZ","year":"2022","unstructured":"RAM\u00edREZ MONTANARINR, AGGARWAL R. Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection [J]. J Hepatol. 2022;77(2):332\u201343.","journal-title":"J Hepatol"},{"issue":"8","key":"3055_CR7","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1128\/JVI.02844-06","volume":"81","author":"C Boni","year":"2007","unstructured":"Boni C, Fisicaro P, Valdatta C, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol. 2007;81(8):4215\u201325.","journal-title":"J Virol"},{"issue":"2","key":"3055_CR8","doi-asserted-by":"publisher","first-page":"267","DOI":"10.3760\/cma.j.issn.0366-6999.20120535","volume":"126","author":"H MA","year":"2013","unstructured":"MA H, ZHANG H H WEIL. Frequency of T-cell FoxP3\u207a Treg and CD4\u207a\/CD8\u207a PD-1 expression is related to hbeag seroconversion in hepatitis B patients on pegylated interferon [J]. Chin Med J (Engl). 2013;126(2):267\u201373.","journal-title":"Chin Med J (Engl)"},{"issue":"3","key":"3055_CR9","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.cld.2010.05.012","volume":"14","author":"CHANG K M","year":"2010","unstructured":"CHANG K M. Hepatitis B immunology for clinicians [J]. Clin Liver Dis. 2010;14(3):409\u201324.","journal-title":"Clin Liver Dis"},{"issue":"1","key":"3055_CR10","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1136\/gutjnl-2021-325915","volume":"72","author":"C Zhang","year":"2023","unstructured":"Zhang C, Li J, Cheng Y, et al. Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients. Gut. 2023;72(1):153\u201367.","journal-title":"Gut"},{"issue":"10","key":"3055_CR11","doi-asserted-by":"publisher","first-page":"4588","DOI":"10.1172\/JCI121960","volume":"128","author":"AR Burton","year":"2018","unstructured":"Burton AR, Pallett LJ, Mccoy LE, et al. Circulating and intrahepatic antiviral B cells are defective in hepatitis B. J Clin Invest. 2018;128(10):4588\u2013603.","journal-title":"J Clin Invest"},{"issue":"9","key":"3055_CR12","doi-asserted-by":"publisher","first-page":"e2451085","DOI":"10.1002\/eji.202451085","volume":"54","author":"OSMANI","year":"2024","unstructured":"OSMANI, Z, VILLANUEVA M A, JOSEPH-CHAZAN J, et al. Intrahepatic plasma cells, but not atypical memory B cells, associate with clinical phases of chronic hepatitis B [J]. Eur J Immunol. 2024;54(9):e2451085.","journal-title":"Eur J Immunol"},{"issue":"1","key":"3055_CR13","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2025.2463569","volume":"57","author":"L Tan","year":"2025","unstructured":"Tan L, Mo Z, Gan W, et al. The remodeling of B-cell subsets was correlated with the clearance of hepatitis B antigen during pegylated IFN \u03b1-2a therapy in CHB patients. Ann Med. 2025;57(1):2463569.","journal-title":"Ann Med"},{"issue":"1","key":"3055_CR14","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.jhep.2020.01.024","volume":"73","author":"T Vanwolleghem","year":"2020","unstructured":"Vanwolleghem T, Groothuismink ZMA, Kreefft K, et al. Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV. J Hepatol. 2020;73(1):52\u201361.","journal-title":"J Hepatol"},{"issue":"4","key":"3055_CR15","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1007\/s12072-025-10846-y","volume":"19","author":"J Li","year":"2025","unstructured":"Li J, Chen S, Zhen C, et al. Single-cell transcriptomic profiling reveals dysregulation of B-cell subset function in patients with chronic hepatitis B. Hepatol Int. 2025;19(4):760\u2013772. https:\/\/doi.org\/10.1007\/s12072-025-10846-y","journal-title":"Hepatol Int"},{"issue":"6","key":"3055_CR16","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.jhep.2024.06.033","volume":"81","author":"JW Zhang","year":"2024","unstructured":"Zhang JW, Lai RM, Wang LF, et al. Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B. J Hepatol. 2024;81(6):960\u201370.","journal-title":"J Hepatol"},{"issue":"1","key":"3055_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0467-4","volume":"9","author":"A Haque","year":"2017","unstructured":"Haque A, Engel J, Teichmann SA, et al. A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications. Genome Med. 2017;9(1):75.","journal-title":"Genome Med"},{"key":"3055_CR18","doi-asserted-by":"crossref","unstructured":"EASL. 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection [J]. J Hepatol, 2017, 67(2): 370\u2009\u2013\u200998.","DOI":"10.1016\/j.jhep.2017.03.021"},{"issue":"2","key":"3055_CR19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao Y, Stuart T, Kowalski MH, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2024;42(2):293\u2013304.","journal-title":"Nat Biotechnol"},{"issue":"12","key":"3055_CR20","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, Millard N, Fan J, et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019;16(12):1289\u201396.","journal-title":"Nat Methods"},{"issue":"D1","key":"3055_CR21","doi-asserted-by":"publisher","first-page":"D870","DOI":"10.1093\/nar\/gkac947","volume":"51","author":"C Hu","year":"2023","unstructured":"Hu C, Li T, Xu Y, et al. CellMarker 2.0: an updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data. Nucleic Acids Res. 2023;51(D1):D870-d6.","journal-title":"Nucleic Acids Res"},{"issue":"7735","key":"3055_CR22","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/s41586-018-0694-x","volume":"564","author":"L Zhang","year":"2018","unstructured":"Zhang L, Yu X, Zheng L, et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature. 2018;564(7735):268\u201372.","journal-title":"Nature"},{"issue":"1","key":"3055_CR23","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","volume":"20","author":"S Jin","year":"2025","unstructured":"Jin S, Plikus MV, Nie Q. CellChat for systematic analysis of cell-cell communication from single-cell transcriptomics. Nat Protoc. 2025;20(1):180\u2013219.","journal-title":"Nat Protoc"},{"issue":"3","key":"3055_CR24","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu T, Hu E, Xu S, et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation (Camb). 2021;2(3):100141.","journal-title":"Innovation (Camb)"},{"issue":"2","key":"3055_CR25","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/cei.13615","volume":"205","author":"Y Li","year":"2021","unstructured":"Li Y, Li Z, Hu F. Double-negative (DN) B cells: an under-recognized effector memory B cell subset in autoimmunity. Clin Exp Immunol. 2021;205(2):119\u201327.","journal-title":"Clin Exp Immunol"},{"key":"3055_CR26","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev-immunol-041015-055531","volume":"35","author":"F Weisel","year":"2017","unstructured":"Weisel F, Shlomchik M. Memory B cells of mice and humans. Annu Rev Immunol. 2017;35:255\u201384.","journal-title":"Annu Rev Immunol"},{"key":"3055_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02673","volume":"9","author":"SF Brynjolfsson","year":"2018","unstructured":"Brynjolfsson SF, Persson Berg L, Olsen Ekerhult T, et al. Long-lived plasma cells in mice and men. Front Immunol. 2018;9:2673.","journal-title":"Front Immunol"},{"issue":"5","key":"3055_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102482","volume":"24","author":"A Rouers","year":"2021","unstructured":"Rouers A, Appanna R, Chevrier M. CD27hiCD38hi plasmablasts are activated B cells of mixed origin with distinct function. iScience. 2021;24(5):102482.","journal-title":"iScience"},{"issue":"1","key":"3055_CR29","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jdermsci.2018.11.008","volume":"93","author":"MATSUSHITA T","year":"2019","unstructured":"MATSUSHITA T. Regulatory and effector B cells: friends or foes? [J]. J Dermatol Sci. 2019;93(1):2\u20137.","journal-title":"J Dermatol Sci"},{"key":"3055_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1488527","volume":"14","author":"F Yu","year":"2024","unstructured":"Yu F, Zhu Y, Li S. Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies. Front Cell Infect Microbiol. 2024;14:1488527.","journal-title":"Front Cell Infect Microbiol"},{"key":"3055_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.759292","volume":"8","author":"X Jin","year":"2021","unstructured":"Jin X, Yan ZH, Lu L. Peripheral immune cells exhaustion and functional impairment in patients with chronic hepatitis B. Front Med. 2021;8:759292.","journal-title":"Front Med"},{"issue":"1","key":"3055_CR32","doi-asserted-by":"publisher","first-page":"2475847","DOI":"10.1080\/22221751.2025.2475847","volume":"14","author":"B Jiang","year":"2025","unstructured":"Jiang B, Guan G, Zhao K, et al. Mechanisms underlying delayed loss of HBeAg and HBV DNA following HBsAg seroclearance in PEG-IFN\u03b1 treated patients of chronic hepatitis B. Emerg Microbes Infect. 2025;14(1):2475847. https:\/\/doi.org\/10.1080\/22221751.2025.2475847","journal-title":"Emerg Microbes Infect"},{"key":"3055_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1474853","volume":"15","author":"D Dey","year":"2024","unstructured":"Dey D, Biswas S, Pal S. Monocyte-derived galectin-9 and PD-L1 differentially impair adaptive and innate immune response in chronic HBV infection and their expression remain unaltered after antiviral therapy. Front Immunol. 2024;15:1474853.","journal-title":"Front Immunol"},{"issue":"10","key":"3055_CR34","doi-asserted-by":"publisher","first-page":"e0090924","DOI":"10.1128\/spectrum.00909-24","volume":"12","author":"C WANG","year":"2024","unstructured":"WANG C, HUANG C, LI Y, et al. Hepatitis B surface antigen impairs TLR4 signaling by upregulating A20 expression in monocytes [J]. Microbiol Spectr. 2024;12(10):e0090924.","journal-title":"Microbiol Spectr"},{"issue":"5","key":"3055_CR35","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1007\/s12026-024-09495-4","volume":"72","author":"X Wu","year":"2024","unstructured":"Wu X, Zhao W, Miao Q. CCR2+TREM-1+ monocytes promote natural killer T cell dysfunction contributing towards HBV disease progression. Immunol Res. 2024;72(5):938\u201347.","journal-title":"Immunol Res"},{"key":"3055_CR36","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1146\/annurev-immunol-042617-053119","volume":"37","author":"PB Narasimhan","year":"2019","unstructured":"Narasimhan PB, Marcovecchio P, Hamers AAJ. Nonclassical monocytes in health and disease. Annu Rev Immunol. 2019;37:439\u201356.","journal-title":"Annu Rev Immunol"},{"key":"3055_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.891424","volume":"13","author":"W Cao","year":"2022","unstructured":"Cao W, Xie S, Zhang L, et al. Expression of functional molecule on plasmacytoid dendritic cells is associated with HBsAg loss in HBeAg-positive patients during PEG-IFN \u03b1-2a treatment. Front Immunol. 2022;13:891424.","journal-title":"Front Immunol"},{"issue":"12","key":"3055_CR38","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1038\/s41423-022-00939-1","volume":"19","author":"H Zhao","year":"2022","unstructured":"Zhao H, Yu Y, Wang Y, et al. Cholesterol accumulation on dendritic cells reverses chronic hepatitis B virus infection-induced dysfunction. Cell Mol Immunol. 2022;19(12):1347\u201360.","journal-title":"Cell Mol Immunol"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-025-03055-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-03055-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-03055-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:56:20Z","timestamp":1769435780000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12985-025-03055-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,20]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3055"],"URL":"https:\/\/doi.org\/10.1186\/s12985-025-03055-4","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,20]]},"assertion":[{"value":"10 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The data in this study can be openly accessed from public databases and do not require ethical review.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}