The immune landscape and mechanism of hepatitis B virus surface antigen clearance [RNA-Seq]

Hepatitis B virus (HBV) surface antigen (HBsAg) clearance constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic hepatitis B. Here, we reveal the immunological landscape and mechanism of HBsAg clearance in mice. After acquiring nonopsonized HBsAg, B cells prime CD4+ T cell responses by CCR5- and EBI2-guided interaction with CD4+ T cells at follicular and interfollicular regions, respectively. Monocyte-derived macrophages transport complement-opsonized HBsAg to follicular dendritic cells (FDCs) to maintain germinal center reaction. Batf3+ XCR1+ conventional type 1 DCs (cDC1s) acquire and present HBsAg by MHC-I cross-dressing to drive CD8+ T cell responses in liver. We map the antigen-presenting cell (APC)-T cell crosstalk landscape and identify key costimulatory signals. The immune responses in patients with acute HBV infection are revealed by a single-cell transcriptome atlas. These findings revolutionize our understanding of anti-HBV immune responses and would lead to immunotherapeutic strategies for HBsAg clearance.