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PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection
Loghman Salimzadeh,1,2,3 Nina Le Bert,1 Charles-A. Dutertre,1,2 Upkar S. Gill,4 Evan W. Newell,2 Christian Frey,5 Magdeleine Hung,5 Nikolai Novikov,5 Simon Fletcher,5 Patrick T.F. Kennedy,4 and Antonio Bertoletti1,2
First published August 7, 2018 - More info
Related 1 article:
Entering the spotlight: hepatitis B surface antigen–specific B cells
Christoph Neumann-Haefelin, Robert Thimme
Category: Commentary
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.
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