Open AccessHepatitis B virus‐induced hyperactivation of B cells in chronic hepatitis B patients via TLR4
Author(s) -
Li Yang,
Yin Shengxia,
Chen Yuxin,
Zhang Quan,
Huang Rui,
Jia Bei,
Jie Wei,
Yao Kefang,
Wang Jian,
Tong Xin,
Liu Yong,
Wu Chao
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15202
Subject(s) - hyperactivation , hepatitis b virus , tlr4 , hepatitis b , b cell , biology , cd19 , cell , virus , virology , immunology , cancer research , immune system , antibody , biochemistry
B cell hyperactivation and functional impairment were identified from patients with chronic hepatitis B virus (CHB) infection; however, the underlying mechanism remains unknown. Here, we aim to elucidate the mechanisms responsible for B cell hyperactivation during HBV infection. Peripheral CD19 + B cells isolated from 4 CHB patients and 4 healthy volunteers were analysed by RNA sequencing. A total of 1401 differentially expressed genes were identified from B cell transcriptome of CHB patients vs healthy volunteers. We found that B cells from CHB patients were functional impaired, with increased TLR4 expression, activated NF‐κB pathway and altered mitochondrial function. The expression of B cell activation‐related genes, including TLR4, was further validated using additional clinical samples. To further verify the role of TLR4 in B cell activation during CHB, B cell phenotypes were determined in wild‐type (WT) and TLR4 −/− HBV‐carrier mice. Hyperactivated B cell and TLR4 signalling pathway were observed in WT HBV‐carrier mice, while TLR4 ablation failed to induce B cell hyperactivation, and downstream MyD88 and NF‐κB were also not altered. Taken together, TLR4 pathway plays a pivotal role in B cell hyperactivation during CHB, which might serve as a promising target for B cell function restoration.