B CELL IMMUNITY IN HBV INFECTION

Abstract

The development of antibodies against the Hepatitis B virus (HBV) surface antigen(HBsAg) constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic HBV infection (CHB). CHB is known to suppress virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a new method for direct ex vivo detection of HBsAg-specific memory B cells (MBCs) and analyzing their frequency, function and phenotype utilizing fluorescently labeled HBsAg “baits”. We found that frequencies of circulating HBsAg-specific MBCs are independent of the HBV infection status. In contrast, serum HBsAg presence affects function and phenotype of HBsAg-specific MBCs that were unable to mature in vitro into antibody-secreting cells and displayed characteristics of atypical MBCs. HBsAg-specific MBCs maturation could be partially restored by a method involving the combination of IL-2, IL-21 and CD40L-expressing feeder cells, and further boosted by addition of anti-PD-1.