[HTML][HTML] PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection

L Salimzadeh, N Le Bert, CA Dutertre… - The Journal of …, 2018 - Am Soc Clin Investig
L Salimzadeh, N Le Bert, CA Dutertre, US Gill, EW Newell, C Frey, M Hung, N Novikov…
The Journal of clinical investigation, 2018Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation