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.