Regulatory Role of B Cells and Its Subsets in Hepatitis E Virus Infection

Antibodies as well as memory B cells are the potential correlates of a protective immune response against hepatitis E virus (HEV) infection. Literature on the role of B regulatory cells (Bregs) in acute viral infections is limited. We have evaluated the role of IL-10 expressing Bregs in HEV infection. A total of 108 acute hepatitis E patients, 55 hepatitis E recovered individuals and 128 HEV naïve healthy controls were enrolled. The percentages of peripheral CD19⁺, immature CD19⁺CD24^hiCD38^hi, mature CD19⁺CD24^intCD38^int and memory CD19⁺CD24^hiCD38^- B cells were analyzed by flowcytometry. Intracellular cytokine staining for IL-10 and TGF-β, HEV-rORF2p specific T cell response (IFN-γ expression) pre/post IL-10/IL-10R blocking and CD19⁺IL-10⁺ B cells-depletion based assays were carried out to assess the functionality of Bregs. The percentage of HEV-rORF2p specific immature B cell phenotype was significantly higher in acute hepatitis E patients compared to hepatitis E recovered individuals and controls. Significantly higher IL-10 expression on B and HEV-rORF2p stimulated immature B cells of acute hepatitis E patients compared to controls indicated that Bregs are functional and HEV-rORF2p specific. Enhanced IFN-γ expression on CD8⁺ T cells upon IL-10/IL-10R blocking and also post CD19⁺IL-10⁺ B cells depletion suggested that CD3⁺CD8⁺IFN-γ ⁺ T cells corroborate the regulatory potential of Bregs via IL-10 dependent mechanism. We have identified HEV specific functional, immature CD19⁺CD24^hiCD38^hi B cells having IL-10 mediated regulatory activities and a potential to modulate IFN-γ mediated T cell response in Hepatitis E. The prognostic/pathogenic role of Bregs in recovery from severe hepatitis E needs evaluation.