Association of PD-1+ B cells and IgG+ plasma cells with clinical cure of hepatitis B following interferon therapy

Previous studies by our group and others have demonstrated that pegylated interferon (PEG-IFN) therapy results in a relatively high rate of clinical cure in inactive hepatitis B surface antigen carriers (IHCs). Emerging evidence suggests that B lymphocytes play a pivotal role in HBsAg clearance. This study aimed to evaluate the efficacy of PEG-IFN in IHCs, investigate dynamic changes in global (non-HBV-specific) B-cell subset frequencies and their association with HBsAg clearance, and characterize the immunological profiles of B cells in CHB patients who achieved a functional cure. A total of 458 inactive IHCs who were enrolled at Beijing You’an Hospital, Capital Medical University, between January 2008 and February 2023 were included in this study. All participants received once-weekly subcutaneous injections of PEG-IFNα-2b, and clinical outcomes were retrospectively analyzed in the entire cohort. B-cell phenotyping was performed in a subset of 36 patients (21 with HBsAg clearance and 15 without) to assess the frequencies of PD-1⁺ and IgG⁺ B-cell subsets, including total B cells, plasmablasts, naïve B cells, immature B cells, and memory B cells. These assessments were conducted at baseline and at weeks 12 and 24 of treatment. Clinical cure rates were 15.98% at week 24 and 28.27% at week 48 of PEG-IFN therapy. At week 24, the frequency of PD-1⁺ total B cells was significantly lower in the C group than in the NC group (0.63% vs. 1.61%, P = 0.037). The proportion of IgG⁺ plasmablasts was significantly higher in the C group compared to the NC group (10% vs. 5.5%, P = 0.016). IHCs who achieved HBsAg clearance under PEG-IFN therapy had lower PD-1⁺ total B-cell frequencies and relatively higher proportions of IgG⁺ plasmablasts than those without clearance. These findings show limited observational differences in PD-1⁺ B-cell and IgG⁺ plasmablast frequencies between groups, which may be associated with clinical cure, but the biological implications remain uncertain and warrant confirmation in larger mechanistic studies.