Characterization of intrahepatic B cells in acuteon-chronic liver failure
Characterization of intrahepatic B cells in acuteon-chronic liver failure
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DOI：
10.3389/fimmu.2022.1041176
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发表时间：
2022
影响因子：
7.3
通讯作者：
Xiaosong Chen
中科院分区：
文献类型：
--
作者：
Yudong Zhao;Wei He;Chenchen Wang;Nana Cui;Changjie Yang;Zhengrui You;Bisheng Shi;Lei Xia;Xiaosong Chen
Background and objectives: Acute 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..Methods: Paired 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..Results: In 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 Bcells were in positive association with disease severity indices including alkaline.phosphatase and gamma-glutamyl transferase..Conclusions: In 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.
