Z Gastroenterol 2011; 49 - P351
DOI: 10.1055/s-0031-1285621

CD20+ B cell infiltration in a mouse model for HBV-associated liver fibrosis depends on genetic background

J Stiefel 1, Y Churin 1, M Roderfeld 1, K Kopsch 1, D Glebe 2, E Roeb 1
  • 1Justus Liebig Universität Gießen, Medizinische Klinik II, Schwerpunkt Gastroenterologie, Gießen, Germany
  • 2Justus Liebig Universität Gießen, Institut für Virologie, Gießen, Germany

Introduction: Chronic hepatitis B virus (HBV) infection is associated with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Mouse models that mimic many of the pathological events of HBV mediated liver fibrosis are yet not well understood. We examined transgenic (tg) mice which overproduce the HBV large envelope polypeptide for liver fibrosis with different genetic background – C57BL/6 and BALB/c. Since the impact of B-cells could be demonstrated in a CCl4-induced model of fibrosis1 our aim was to analyse B cells in the liver of HBV-transgenic mice.

Methods: C57BL/6 versus BALB/c transgenic mice producing HBV large envelope polypeptide and hepatitis B surface antigen (HBsAg) in the liver and their non-transgenic littermates were sacrificed at different time points after birth (3, 6 and 12 months). The extent of liver injury was examined by serum alanine transaminase (ALT) activity. Hepatic fibrosis was estimated by Sirius Red staining and measurement of collagen expression by real-time PCR. Recruitment of T and B lymphocytes was studied using anti-CD3 and anti-CD20 antibody, respectively.

Results: ALT activity was higher in tg mice on both genetic backgrounds compared to corresponding littermates. Histological and immunofluorescence analyses of liver tissue revealed significant inflammation and fibrosis in tg mice. Interestingly we observed a more prominent fibrosis in tg (BALB/c) compared to tg (C57BL/6). Both, BALB/c-tg and C57BL/6-tg mice, showed heightened B and T cell infiltration compared to non-transgenic littermates in the liver. However, the number of CD20-positive cells was significantly increased in tg (BALB/c) compared to tg (C57BL/6).

Conclusions:

  • Tg (BALB/c) seems to be more appropriate to study fibrosis than tg (C57BL/6) model.

  • B and T cells infiltrate the liver of HBV-transgenic mice.

  • Development of more prominent fibrosis in tg (BALB/c) correlates with increased amounts of B cells in the liver.

1Novobrantseva TI, Majeau GR, Amatucci A et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest 2005; 115: 3072–3082.