Zhu Dan, Du Yanqin, Zhao Mengxiao, Ablikim Dilhumare, Huang Hongming, Pan Wen, Zeng Xiaoqing, Xu Chunli, Lu Mengji, Sutter Kathrin, Dittmer Ulf, Zheng Xin, Yang Dongliang, Liu Jia
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hepatol Int. 2025 Feb;19(1):93-105. doi: 10.1007/s12072-024-10753-8. Epub 2024 Dec 4.
The pivotal role of antibody-producing B cells in controlling hepatitis B virus (HBV) infection is well-established. However, the antiviral role of B cells extends beyond antibody production, which has been insufficiently studied for HBV infection.
Using an HBV hydrodynamic injection (HDI) mouse model with B cell depletion or functional blockade, we detected HBV infection markers and assessed T cell function through enzyme-linked immunosorbent assay, RT-PCR and flow cytometry.
We observed significantly delayed serum and intrahepatic HBV clearance in permanently B cell-deficient and transiently B cell-depleted mice as well as mice with a functional B cell blockade. Blocking B cell function prior to or soon after HBV HDI resulted in delayed HBV clearance indicating that B cells contribute to initiating anti-HBV immune responses after following HBV exposure. Additionally, we also found an early activation of B cells following HBV exposure, characterized by an upregulation of MHC-II, CXCR5, and PD-1. Critically, the proliferation and activation of both CD4 + and CD8 + T cells were impaired after B cell depletion prior to HBV challenge. Consistently, depleting B cells reduced the generation of Th1, Th2, and Th17 cells in the spleen and hindered HBV-specific CD8 + T cell responses in the liver. Along these lines, the HBV-exposed B cells were more efficient in inducing HBcAg-specific CD8 + T cell responses in vitro.
Collectively, our data indicate that B cells, in addition to antibody production, are essential for the development of anti-HBV cellular responses and intrahepatic HBV clearance during the early stage of HBV antigen exposure.
产生抗体的B细胞在控制乙型肝炎病毒（HBV）感染中起关键作用，这一点已得到充分证实。然而，B细胞的抗病毒作用不仅限于产生抗体，对于HBV感染，这方面的研究还不够充分。
我们使用B细胞耗竭或功能阻断的HBV水动力注射（HDI）小鼠模型，通过酶联免疫吸附测定、逆转录聚合酶链反应和流式细胞术检测HBV感染标志物并评估T细胞功能。
我们观察到，在永久性B细胞缺陷、短暂性B细胞耗竭的小鼠以及具有功能性B细胞阻断的小鼠中，血清和肝内HBV清除明显延迟。在HBV HDI之前或之后不久阻断B细胞功能会导致HBV清除延迟，这表明B细胞在接触HBV后有助于启动抗HBV免疫反应。此外，我们还发现HBV暴露后B细胞早期激活，其特征是MHC-II、CXCR5和PD-1上调。至关重要的是，在HBV攻击前B细胞耗竭后，CD4 +和CD8 + T细胞的增殖和激活均受损。一致的是，B细胞耗竭减少了脾脏中Th1、Th2和Th17细胞的生成，并阻碍了肝脏中HBV特异性CD8 + T细胞反应。同样，暴露于HBV的B细胞在体外诱导HBcAg特异性CD8 + T细胞反应方面更有效。
总体而言，我们的数据表明，除了产生抗体外，B细胞对于HBV抗原暴露早期抗HBV细胞反应的发展和肝内HBV清除至关重要。
