PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection.
dc.contributor.author | Salimzadeh, L | en_US |
dc.contributor.author | Le Bert, N | en_US |
dc.contributor.author | Dutertre, C-A | en_US |
dc.contributor.author | Gill, US | en_US |
dc.contributor.author | Newell, EW | en_US |
dc.contributor.author | Frey, C | en_US |
dc.contributor.author | Hung, M | en_US |
dc.contributor.author | Novikov, N | en_US |
dc.contributor.author | Fletcher, S | en_US |
dc.contributor.author | Kennedy, PT | en_US |
dc.contributor.author | Bertoletti, A | en_US |
dc.date.accessioned | 2019-02-22T17:37:23Z | |
dc.date.available | 2018-07-26 | en_US |
dc.date.issued | 2018-10-01 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/55509 | |
dc.description.abstract | Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as "baits" for specific ex vivo detection of HBsAg-specific B cells and analysis of their quantity, function, and phenotype. We studied healthy vaccinated subjects (n = 18) and patients with resolved (n = 21), acute (n = 11), or chronic (n = 96) HBV infection and observed that frequencies of circulating HBsAg-specific B cells were independent of HBV infection status. In contrast, the presence of serum HBsAg affected function and phenotype of HBsAg-specific B cells that were unable to mature in vitro into Ab-secreting cells and displayed an increased expression of markers linked to hyperactivation (CD21lo) and exhaustion (PD-1). Importantly, B cell alterations were not limited to HBsAg-specific B cells, but affected the global B cell population. HBsAg-specific B cell maturation could be partially restored by a method involving the combination of the cytokines IL-2 and IL-21 and CD40L-expressing feeder cells and was further boosted by the addition of anti-PD-1 Abs. In conclusion, HBV infection has a marked impact on global and HBV-specific humoral immunity, yet HBsAg-specific B cells are amenable to a partial rescue by B cell-maturing cytokines and PD-1 blockade. | en_US |
dc.format.extent | 4573 - 4587 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | J Clin Invest | en_US |
dc.subject | B cells | en_US |
dc.subject | Hepatitis | en_US |
dc.subject | Hepatology | en_US |
dc.subject | Infectious disease | en_US |
dc.title | PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1172/JCI121957 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30084841 | 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 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
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Centre for Immunobiology [1121]