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Hepatitis B virus‐induced hyperactivation of B cells in chronic hepatitis B patients via TLR4
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294113/ https://www.ncbi.nlm.nih.gov/pubmed/32391647 http://dx.doi.org/10.1111/jcmm.15202 |
Sumario: | 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. |
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