dc.contributor.author | Burton, AR | |
dc.contributor.author | Pallett, LJ | |
dc.contributor.author | McCoy, LE | |
dc.contributor.author | Suveizdyte, K | |
dc.contributor.author | Amin, OE | |
dc.contributor.author | Swadling, L | |
dc.contributor.author | Alberts, E | |
dc.contributor.author | Davidson, BR | |
dc.contributor.author | Kennedy, PT | |
dc.contributor.author | Gill, US | |
dc.contributor.author | Mauri, C | |
dc.contributor.author | Blair, PA | |
dc.contributor.author | Pelletier, N | |
dc.contributor.author | Maini, MK | |
dc.date.accessioned | 2019-02-25T09:06:09Z | |
dc.date.available | 2018-07-26 | |
dc.date.available | 2019-02-25T09:06:09Z | |
dc.date.issued | 2018-08-09 | |
dc.identifier.citation | J Clin Invest. 2018;128(10):4588-4603. https://doi.org/10.1172/JCI121960 | en_US |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/55523 | |
dc.description.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. | en_US |
dc.description.sponsorship | Roche/UCL Impact Studentship (to ARB) | en_US |
dc.description.sponsorship | Medical Research Council grant (G0801213) | en_US |
dc.description.sponsorship | Wellcome Trust Senior Investigator Award (101849/Z/13/A to MKM) | en_US |
dc.format.extent | 4588 - 4603 | |
dc.language | eng | |
dc.language.iso | en_US | en_US |
dc.publisher | American Society for Clinical Investigation | en_US |
dc.relation.ispartof | J Clin Invest | |
dc.rights | This work is licensed under the Creative Commons Attribution 4.0 International License. | |
dc.subject | B cells | en_US |
dc.subject | Hepatitis | en_US |
dc.subject | Immunology | en_US |
dc.subject | Infectious disease | en_US |
dc.subject | Tolerance | en_US |
dc.title | Circulating and intrahepatic antiviral B cells are defective in hepatitis B. | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2018 Burton et al. | |
dc.identifier.doi | 10.1172/JCI121960 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30091725 | en_US |
pubs.issue | 10 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 128 | en_US |
dcterms.dateAccepted | 2018-07-26 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |