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

摘要

Objectives: Dissecting the underlying mechanism of T cells remodeling mediated by interferon alpha (IFN-alpha) 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-alpha-mediated anti-hepatitis B virus (HBV) cellular immunity. Method: The effects of B cells on IFN-alpha-mediated T cell response were investigated in B cell-deficient mouse model with HBV and IFN-alpha 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-alpha-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-alpha 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 alpha-reinforced connections of B cells toward T cells as mediated by the antigen presentation and costimulatory functions in B cells. Conclusion: IFN-alpha orchestrates protective HBV-specific cellular immunity in a B cell-dependent manner.

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