Hepatitis B virus‐induced hyperactivation of B cells in chronic hepatitis B patients via TLR4

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Abstract
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.
Funding Information
  • Nanjing Medical Science and Technique Development Foundation (QRX17121)
  • Jiangsu Science and Technology Development Plan (BE2017605)
  • Medical Science and Technology Development Foundation of Nanjing (YKK16118)
  • Natural Science Foundation of Jiangsu Province for Young Scholar (BK20160121)
  • National Natural Science Foundation of China (81672025, 81501749, 81600201, 81702011)
  • Jiangsu Provincial Medical Innovation Team (CXTDA2017005)
  • Foundation project of Jiangsu Commission of Health (Q2017003)
  • Jiangsu Provincial Young Medical Talent (QNR2016007)
  • Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health (ZDX16004)

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