Characterization of intrahepatic B cells in acute-on-chronic liver failure
Background and objectivesAcute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B ce...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1041176/full |
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| author | Yudong Zhao Wei He Chenchen Wang Nana Cui Changjie Yang Zhengrui You Bisheng Shi Lei Xia Xiaosong Chen |
| author_facet | Yudong Zhao Wei He Chenchen Wang Nana Cui Changjie Yang Zhengrui You Bisheng Shi Lei Xia Xiaosong Chen |
| author_sort | Yudong Zhao |
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| description | Background and objectivesAcute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.MethodsPaired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19+ and CD138+ on liver tissues was examined by immunohistochemistry staining.ResultsIn this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27+CD21− activated memory B cells (AM), CD27−CD21− atypical memory B cells (atMBC), CD27+IgD−IgM+(IgM+ memory B cells), and CD27+CD38++ plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27+CD38++plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.ConclusionsIn this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy. |
| format | Article |
| id | doaj-art-abbf8010612a4c39bba636ff35a5d36f |
| institution | OA Journals |
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| publishDate | 2022-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-abbf8010612a4c39bba636ff35a5d36f2025-08-20T02:28:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10411761041176Characterization of intrahepatic B cells in acute-on-chronic liver failureYudong Zhao0Wei He1Chenchen Wang2Nana Cui3Changjie Yang4Zhengrui You5Bisheng Shi6Lei Xia7Xiaosong Chen8Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDivision of Gastroenterology and Hepatology , Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, National Health Council (NHC) Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDivision of Gastroenterology and Hepatology , Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, National Health Council (NHC) Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDivision of Gastroenterology and Hepatology , Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, National Health Council (NHC) Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaBackground and objectivesAcute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.MethodsPaired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19+ and CD138+ on liver tissues was examined by immunohistochemistry staining.ResultsIn this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27+CD21− activated memory B cells (AM), CD27−CD21− atypical memory B cells (atMBC), CD27+IgD−IgM+(IgM+ memory B cells), and CD27+CD38++ plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27+CD38++plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.ConclusionsIn this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1041176/fullacute on chronic liver failureatypical memory B cellsplasma cellsintrahepatic B cellsdysfunction |
| spellingShingle | Yudong Zhao Wei He Chenchen Wang Nana Cui Changjie Yang Zhengrui You Bisheng Shi Lei Xia Xiaosong Chen Characterization of intrahepatic B cells in acute-on-chronic liver failure Frontiers in Immunology acute on chronic liver failure atypical memory B cells plasma cells intrahepatic B cells dysfunction |
| title | Characterization of intrahepatic B cells in acute-on-chronic liver failure |
| title_full | Characterization of intrahepatic B cells in acute-on-chronic liver failure |
| title_fullStr | Characterization of intrahepatic B cells in acute-on-chronic liver failure |
| title_full_unstemmed | Characterization of intrahepatic B cells in acute-on-chronic liver failure |
| title_short | Characterization of intrahepatic B cells in acute-on-chronic liver failure |
| title_sort | characterization of intrahepatic b cells in acute on chronic liver failure |
| topic | acute on chronic liver failure atypical memory B cells plasma cells intrahepatic B cells dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1041176/full |
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