B-Cell Activation Gene Signature in Blood and Liver of Hepatitis B e Antigen-Positive Patients With Immune Active Chronic Hepatitis B

Background Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and liver of patients with chronic HBV.Methods RNA-sequencing and flow cytometric analysis was performed on peripheral blood B cells of patients with immune active chronic HBV, comparing them with samples from healthy controls. In addition, gene expression profiles of B cells in the liver were analyzed by bulk and single-cell RNA-seq.Results Our data show a distinctive B-cell activation gene signature in the blood of patients with immune active chronic HBV, characterized by a significant upregulation of immune-related genes. This peripheral activation profile was also observed in B cells from the liver by single-cell RNA-seq, with naive and memory B-cell subsets being the primary carriers of the signature.Conclusions Our findings suggest that B-cell gene profiles reflect responsiveness to HBV infection; these findings are relevant for clinical studies evaluating immunomodulatory treatment strategies for HBV. The role of B cells in controlling chronic hepatitis B virus (HBV) infection is still not well established. We show that, in contrast to other cell types, a distinctive B-cell activation gene signature is found in patients with immune active chronic HBV. Graphical abstract