Functional B cell deficiency promotes intrahepatic HBV replication and impairs the development of anti-HBV T cell responses

Abstract

Background: The pivotal role of antibody-producing B cells in controlling hepatitis B virus (HBV) infection is well-established. However, the antiviral role of B cells extends beyond antibody production, which has been insufficiently studied for HBV infection.

Methods: Using an HBV hydrodynamic injection (HDI) mouse model with B cell depletion or functional blockade, we detected HBV infection markers and assessed T cell function through enzyme-linked immunosorbent assay, RT-PCR and flow cytometry.

Results: We observed significantly delayed serum and intrahepatic HBV clearance in permanently B cell-deficient and transiently B cell-depleted mice as well as mice with a functional B cell blockade. Blocking B cell function prior to or soon after HBV HDI resulted in delayed HBV clearance indicating that B cells contribute to initiating anti-HBV immune responses after following HBV exposure. Additionally, we also found an early activation of B cells following HBV exposure, characterized by an upregulation of MHC-II, CXCR5, and PD-1. Critically, the proliferation and activation of both CD4 + and CD8 + T cells were impaired after B cell depletion prior to HBV challenge. Consistently, depleting B cells reduced the generation of Th1, Th2, and Th17 cells in the spleen and hindered HBV-specific CD8 + T cell responses in the liver. Along these lines, the HBV-exposed B cells were more efficient in inducing HBcAg-specific CD8 + T cell responses in vitro.

Conclusions: Collectively, our data indicate that B cells, in addition to antibody production, are essential for the development of anti-HBV cellular responses and intrahepatic HBV clearance during the early stage of HBV antigen exposure.

Keywords: Antigen presenting; B cells; B220; CD19; CD20; CD4 + T cells; CD8 + T cells; Hepatitis B virus; Hydrodynamic injection; Liver.