ArticleHepatology communications2026
Dysregulated BCR repertoire and metabolic state of HBsAg-specific B cells in chronic hepatitis B revealed by integrated single-cell analysis.
Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHumoral immunity targeting hepatitis B virus (HBV) surface antigen (HBsAg) is critical for viral clearance. However, the phenotypic, repertoire, and metabolic features of HBsAg-specific B cells in chronic hepatitis B (CHB) remain incompletely defined.
methodsHBsAg-specific B cells were enriched using oligonucleotide-tagged antigen probes and profiled by integrated single-cell RNA sequencing (scRNA-seq) and single-cell B cell receptor sequencing (scBCR-seq) in HBeAg-positive CHB patients, convalescent individuals, and vaccinated healthy controls. Key findings were further evaluated in an independent cohort. Recombinant monoclonal antibodies (mAbs) were generated for functional validation, and ex vivo assays were performed to assess the effects of glutamine modulation on B cell responses.
resultsCHB patients exhibited expansion of unswitched memory (USW) and double-negative 1 (DN1) B cell subsets, characterized by impaired immunoglobulin class switching, altered co-stimulatory molecule expression, and increased clonal expansion. B cell receptor (BCR) repertoire analysis revealed biased immunoglobulin heavy chain variable (IGHV) gene usage and elevated somatic hypermutation in specific isotypes. Single-cell metabolic analysis demonstrated increased oxidative phosphorylation (OXPHOS) and reduced glutamine metabolism in CHB HBsAg-specific B cells. Recombinant mAbs showed heterogeneous and conformation-dependent antigen binding, with limited neutralizing activity. In ex vivo assays, glutamine supplementation enhanced antibody production and was associated with reduced OXPHOS signatures and increased interferon signaling, with similar effects observed in total immunoglobulin secretion.
conclusionsHBsAg-specific B cells in CHB display coordinated alterations in subset composition, BCR repertoire, and metabolic state. These findings identify reproducible features of B-cell dysregulation and suggest a potential link between immunometabolic imbalance and impaired humoral responses, providing a framework for further mechanistic investigation.
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