Antibody‐dependent and antibody‐independent uptake of HBsAg across human leucocyte subsets is similar between individuals with chronic hepatitis B virus infection and healthy donors

Summary Maintaining detectable levels of antibodies to hepatitis B surface antigen ( HB sAg) in serum after HB sAg sero‐conversion is the key clinical endpoint indicative of recovery from infection with hepatitis B virus ( HBV ). As HBV ‐infected hepatocytes secrete HB sAg subviral particles in vast excess over HBV virions, detectable hepatitis B surface antibody (anti‐ HB s) titres imply complete elimination of HBV virions as well as HB sAg particles. Although intrahepatic phagocytes, for example Kupffer cells, are thought to mediate clearance of HB sAg via antibody (Ab)‐dependent and Ab‐independent mechanisms, the relative contributions of circulating phagocytic cell types to HB sAg elimination are poorly characterized. Understanding the role of various immune cell subsets in the clearance of HB sAg is important because Ab‐dependent or Ab‐independent phagocytic HB sAg uptake may modulate presentation of HB sAg‐derived epitopes to antigen‐specific T cells and hence plays a critical role in adaptive immunity against HBV . This study aims to characterize phagocytic leucocyte subsets capable of internalizing HB sAg immune complexes ( HB sAg: IC ) or un‐complexed HB sAg particles in whole blood directly ex vivo. The data show that uptake of HB sAg: IC occurs most prominently in monocytes, B cells, dendritic cells and in neutrophils. In contrast, B cells, and to a lesser degree also monocytes, seem to be effective phagocytes for un‐complexed HB sAg. Importantly, a similar pattern of phagocytic HB sAg uptake was observed in blood from chronic hepatitis B ( CHB ) patients compared to healthy controls, suggesting that phagocytosis‐related cellular functions are not altered in the context of CHB .