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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.
Citation Information: J Clin Invest. 2018;128(10):4588-4603. https://doi.org/10.1172/JCI121960.
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
Total citations by year
Citation information
Citations to this article (151)
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Hepatology | 2021 |
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The Association between Obesity and Severity in Patients with Coronavirus Disease 2019: a Retrospective, Single-center Study, Wuhan
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International journal of medical sciences | 2021 |
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Recovery of Memory B-cell Subsets and Persistence of Antibodies in Convalescent COVID-19 Patients
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The American journal of tropical medicine and hygiene | 2021 |
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The association between Fc gamma RIIb expression levels and chronic hepatitis B virus infection progression
J Jin, Y Liu, X Xu, Z Wang, J Niu |
BMC Infectious Diseases | 2021 |
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Undetectable Anti-HBs Antibodies: Need of a Booster Dose for HIV-1-Infected Individuals
Y Bekele, JA Berzofsky, F Chiodi |
Human vaccines | 2021 |
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Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV
Vanwolleghem T, Adomati T, Van Hees S, Janssen HL |
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Virus reactivation in a non-cirrhotic HBV patient requiring liver transplantation after cessation of nucleoside analogue therapy
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Antiviral therapy | 2021 |
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Vaccine responses in ageing and chronic viral infection
Rees-Spear C, McCoy LE |
2021 | |
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Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches
P Fisicaro, V Barili, M Rossi, I Montali, A Vecchi, G Acerbi, D Laccabue, A Zecca, A Penna, G Missale, C Ferrari, C Boni |
Frontiers in immunology | 2020 |
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Adaptive Immune Response against Hepatitis C Virus
J Kemming, R Thimme, C Neumann-Haefelin |
International journal of molecular sciences | 2020 |
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HBV X protein-based therapeutic vaccine accelerates viral antigen clearance by mobilizing monocyte infiltration into the liver in HBV carrier mice
JH Horng, WH Lin, CR Wu, YY Lin, LL Wu, DS Chen, PJ Chen |
Journal of Biomedical Science | 2020 |
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Chronic Viral Infection Promotes Efficient Germinal Center B Cell Responses
B Fallet, Y Hao, M Florova, K Cornille, AV de los Aires, GG Zubani, YI Ertuna, V Greiff, U Menzel, K Hammad, D Merkler, ST Reddy, JC Weill, CA Reynaud, DD Pinschewer |
Cell Reports | 2020 |
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OMIP‐068 : High‐Dimensional Characterization of Global and Antigen‐Specific B Cells in Chronic Infection
K Cascino, M Roederer, T Liechti |
Cytometry Part A | 2020 |
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Efficacy of an Inhibitor of Hepatitis B Virus Expression in Combination With Entecavir and Interferon‐α in Woodchucks Chronically Infected With Woodchuck Hepatitis Virus
S Menne, S Wildum, G Steiner, M Suresh, K Korolowicz, M Balarezo, C Yon, M Murreddu, X Hong, BV Kallakury, R Tucker, S Yang, JA Young, H Javanbakht |
Hepatology Communications | 2020 |
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Role of spleen tyrosine kinase in liver diseases
DW Kurniawan, G Storm, J Prakash, R Bansal |
World journal of gastroenterology : WJG | 2020 |
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Multiple Roles for Hepatitis B and C Viruses and the Host in the Development of Hepatocellular Carcinoma
KJ Wangensteen, KM Chang |
Hepatology | 2020 |
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The Multiple Functions of B Cells in Chronic HBV Infection
Y Cai, W Yin |
Frontiers in immunology | 2020 |
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Expansion of atypical memory B cells is a prominent feature of COVID-19
B Oliviero, S Varchetta, D Mele, S Mantovani, A Cerino, CG Perotti, S Ludovisi, MU Mondelli |
Cellular and Molecular Immunology | 2020 |
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Reversal of Immunity After Clearance of Chronic HCV Infection—All Reset?
H Wedemeyer, T Khera, B Strunz, NK Björkström |
Frontiers in immunology | 2020 |
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The liver as an immunological barrier redefined by single‐cell analysis
Z Stamataki, L Swadling |
Immunology | 2020 |
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Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B
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Serum alanine aminotransferase flares in chronic hepatitis B infection: the good and the bad
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The Lancet Gastroenterology & Hepatology | 2020 |
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Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients
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Scientific Reports | 2020 |
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Hepatitis Delta Virus Acts as an Immunogenic Adjuvant in Hepatitis B Virus-Infected Hepatocytes
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Reproduction | 2020 |
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Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection
Z Meng, Y Chen, M Lu |
Frontiers in immunology | 2020 |
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Hepatitis B virus‐induced hyperactivation of B cells in chronic hepatitis B patients via TLR4
Y Li, S Yin, Y Chen, Q Zhang, R Huang, B Jia, W Jie, K Yao, J Wang, X Tong, Y Liu, C Wu |
Journal of Cellular and Molecular Medicine | 2020 |
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Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers
V Hehle, M Beretta, M Bourgine, M Ait-Goughoulte, C Planchais, S Morisse, B Vesin, V Lorin, T Hieu, A Stauffer, O Fiquet, JD Dimitrov, ML Michel, MN Ungeheuer, C Sureau, S Pol, JP Santo, H Strick-Marchand, N Pelletier, H Mouquet |
Journal of Experimental Medicine | 2020 |
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Research progress in host immune response during hepatitis B virus infection
XQ Yu, XX Zhang |
Chinese Medical Journal | 2020 |
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Reconstitution of T follicular helper-humoral immune axis with elimination of hepatitis C virus
A Khanam, S Kottilil, E Wilson |
Scientific Reports | 2020 |
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Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection
X Li, Q Zhang, W Zhang, G Ye, Y Ma, C Wen, S Gu, L Tang, Y Li |
Journal of Translational Medicine | 2020 |
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Metabolic defects in splenic B cell compartments from patients with liver cirrhosis
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Cell Death and Disease | 2020 |
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Liver Research | 2020 |
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Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated
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Annals of the rheumatic diseases | 2019 |
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HBV Immune-Therapy: From Molecular Mechanisms to Clinical Applications
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International journal of molecular sciences | 2019 |
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Distinct phenotype and function of circulating Vδ1+ and Vδ2+ γδT-cells in acute and chronic hepatitis B
KM Chang, D Traum, JJ Park, S Ho, K Ojiro, DK Wong, AS Wahed, NA Terrault, M Khalili, RK Sterling, HL Janssen, MC Shuhart, DT Lau, LR Roberts, GS Johnson, DE Kaplan, MR Betts, WM Lee, AS Lok, CM Walker |
PLoS pathogens | 2019 |
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B-cell abnormalities in HIV-1 infection: roles for IgG3 and T-bet
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Current Opinion in HIV and AIDS | 2019 |
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Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
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Science Translational Medicine | 2019 |
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Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response
Z Ma, E Zhang, S Gao, Y Xiong, M Lu |
Frontiers in immunology | 2019 |
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Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance
DC Whitacre, CJ Peters, C Sureau, K Nio, F Li, L Su, JE Jones, M Isogawa, M Sallberg, L Frelin, DL Peterson, Milich |
Human Vaccines & Immunotherapeutics | 2019 |
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Meeting the Challenge of Eliminating Chronic Hepatitis B Infection
PA Revill, C Penicaud, C Brechot, F Zoulim |
Genes & development | 2019 |
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HBV-Induced Immune Imbalance in the Development of HCC
Y Chen, Z Tian |
Frontiers in immunology | 2019 |
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Lipoarabinomannan in Active and Passive Protection Against Tuberculosis
M Correia-Neves, C Sundling, A Cooper, G Källenius |
Frontiers in immunology | 2019 |
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Fine‐Tuning TLR‐7‐Based Therapy for Functional HBV Cure
A Bertoletti, NL Bert |
Hepatology Communications | 2019 |
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Human Monoclonal Antibodies as Adjuvant Treatment of Chronic Hepatitis B Virus Infection
A Cerino, S Mantovani, D Mele, B Oliviero, S Varchetta, MU Mondelli |
Frontiers in immunology | 2019 |
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Hepatitis B and HIV-1 2019 IAS Cure Forum: lessons and benefits from interdisciplinary research
Paximadis M, Perez Patrigeon S, Rajasuriar R, Tatoud R, Scully E, Arbuthnot P |
Journal of Virus Eradication | 2019 |
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Entering the spotlight: hepatitis B surface antigen -specific B cells
Christoph Neumann-Haefelin, Robert Thimme |
Journal of Clinical Investigation | 2018 |
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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 |
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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 |
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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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Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
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