B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus–associated acute liver failure

P Farci, G Diaz, Z Chen… - Proceedings of the …, 2010 - National Acad Sciences
P Farci, G Diaz, Z Chen, S Govindarajan, A Tice, L Agulto, S Pittaluga, D Boon, C Yu…
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome
due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms
whereby HBV induces ALF are unknown. Here, we show that liver tissue collected at the
time of liver transplantation in two patients with HBV-associated ALF is characterized by an
overwhelming B cell response apparently centered in the liver with massive accumulation of
plasma cells secreting IgG and IgM, accompanied by complement deposition. We …
Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. Here, we show that liver tissue collected at the time of liver transplantation in two patients with HBV-associated ALF is characterized by an overwhelming B cell response apparently centered in the liver with massive accumulation of plasma cells secreting IgG and IgM, accompanied by complement deposition. We demonstrate that the molecular target of these antibodies is the hepatitis B core antigen (HBcAg); that these anti-bodies display a restricted variable heavy chain (VH) repertoire and lack somatic mutations; and that these two unrelated individuals with ALF use an identical predominant VH gene with unmutated variable domain (IGHV1-3) for both IgG and IgM anti-HBc antibodies, indicating that HBcAg is the target of a germline human VH gene. These data suggest that humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.
National Acad Sciences