Interferon α facilitates anti-HBV cellular immune response in a B cell-dependent manner

Objectives: Dissecting the underlying mechanism of T cells remodeling mediated by interferon α (IFN-α) is indispensable for achieving an optimum therapeutic response in chronic hepatitis B (CHB) patients. However, little is known about B cells in this process. This study aims to elucidate the roles of B cells in IFN-α-mediated anti-hepatitis B virus (HBV) cellular immunity.

Method: The effects of B cells on IFN-α-mediated T cell response were investigated in B cell-deficient mouse model with HBV and IFN-α plasmid hydrodynamic injection. Single-cell RNA sequencing was performed to dissect the crosstalk among B cell and T cell subsets and the underlying molecule and pathway signatures on longitudinal blood samples from IFN-α-treated CHB patients.

Results: B cell depletion impaired the functional T cell subsets, including HBV-specific CD8⁺ T cells, and engendered a delayed HBV clearance. IFN-α treatment boosted the response of HBV-specific CD8⁺ T cells, whereas such effects disappeared in B cell-deficient mice. The underlying mechanisms were associated with IFN-α-reinforced connections of B cells toward T cells as mediated by the antigen presentation and costimulatory functions in B cells.

Conclusion: IFN-α orchestrates protective HBV-specific cellular immunity in a B cell-dependent manner.