Sorted B cell transcriptomes point towards actively regulated B cell responses during ongoing chronic hepatitis B infections

•Four clinical phases describe the natural course of a chronic hepatitis B (CHB) infection.•The immune cells that govern these clinical disease transitions remain unknown.•We performed RNA sequencing on B cells of CHB patients and healthy controls.•We found distinct gene expression profiles between healthy controls and CHB patients.•Our study corroborates an important role for B cells during ongoing CHB infections. The natural course of chronic hepatitis B virus (HBV) infections follows distinct clinical disease phases, characterized by fluctuating levels of serum HBV DNA and ALT. The immune cells and their features that govern these clinical disease transitions remain unknown. In the current study, we performed RNA sequencing on purified B cells from blood (n = 42) and liver (n = 10) of healthy controls and chronic HBV patients. We found distinct gene expression profiles between healthy controls and chronic HBV patients, as evidenced by 190 differentially expressed genes (DEG), but also between the clinical phenotypes of a chronic HBV infection (17–110 DEG between each phase). Numerous immune pathways, including the B cell receptor pathway were upregulated in liver B cells when compared to peripheral B cells. Further investigation of the detected DEG suggested an activation of B cells during HBeAg seroconversion and an active regulation of B cell signalling in the liver.