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Citations to this article

Circulating and intrahepatic antiviral B cells are defective in hepatitis B
Alice R. Burton, … , Nadege Pelletier, Mala K. Maini
Alice R. Burton, … , Nadege Pelletier, Mala K. Maini
Published August 9, 2018
Citation Information: J Clin Invest. 2018;128(10):4588-4603. https://doi.org/10.1172/JCI121960.
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Research Article Immunology Infectious disease Article has an altmetric score of 26

Circulating and intrahepatic antiviral B cells are defective in hepatitis B

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Abstract

B cells are increasingly recognized as playing an important role in the ongoing control of hepatitis B virus (HBV). The development of antibodies against the viral surface antigen (HBV surface antigen [HBsAgs]) constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic HBV (CHB). We characterized B cells directly ex vivo from the blood and liver of patients with CHB to investigate constraints on their antiviral potential. Unexpectedly, we found that HBsAg-specific B cells persisted in the blood and liver of many patients with CHB and were enriched for T-bet, a signature of antiviral potential in B cells. However, purified, differentiated HBsAg-specific B cells from patients with CHB had defective antibody production, consistent with undetectable anti-HBs antibodies in vivo. HBsAg-specific and global B cells had an accumulation of CD21–CD27– atypical memory B cells (atMBC) with high expression of inhibitory receptors, including PD-1. These atMBC demonstrated altered signaling, homing, differentiation into antibody-producing cells, survival, and antiviral/proinflammatory cytokine production that could be partially rescued by PD-1 blockade. Analysis of B cells within healthy and HBV-infected livers implicated the combination of this tolerogenic niche and HBV infection in driving PD-1hiatMBC and impairing B cell immunity.

Authors

Alice R. Burton, Laura J. Pallett, Laura E. McCoy, Kornelija Suveizdyte, Oliver E. Amin, Leo Swadling, Elena Alberts, Brian R. Davidson, Patrick T.F. Kennedy, Upkar S. Gill, Claudia Mauri, Paul A. Blair, Nadege Pelletier, Mala K. Maini

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2009 Total
Citations: 15 19 15 36 34 24 13 4 1 161
Citation information
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Citations to this article in year 2018 (4)

Title and authors Publication Year
Entering the spotlight: hepatitis B surface antigen -specific B cells
Christoph Neumann-Haefelin, Robert Thimme
Journal of Clinical Investigation 2018
PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection
Loghman Salimzadeh, Nina Le Bert, Charles-A. Dutertre, Upkar S. Gill, Evan W. Newell, Christian Frey, Magdeleine Hung, Nikolai Novikov, Simon Fletcher, Patrick T.F. Kennedy, Antonio Bertoletti
Journal of Clinical Investigation 2018
HBV induces inhibitory FcRL receptor on B cells and dysregulates B cell-T follicular helper cell axis
B Poonia, N Ayithan, M Nandi, H Masur, S Kottilil
Scientific Reports 2018
The Era of Immune Checkpoint Therapy: From Cancer to Viral Infection—A Mini Comment on the 2018 Medicine Nobel Prize
J Liu, W Pan, D Yang
Virologica Sinica 2018

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