Single‐Cell Transcriptome Identifies a Proinflammatory B‐Cell Subset in Hepatitis B Virus Associated Acute‐on‐Chronic Liver Failure

ABSTRACT Acute‐on‐chronic liver failure (ACLF) is a severe clinical condition with high short‐term mortality, in part due to the dysfunctional immune response. Identifying immune mechanism under ACLF is critical to understand its pathogenesis and to develop novel targeted therapeutics. Among the immune cells, how are B cells involved in ACLF remains largely unknown. We performed scRNA‐seq on peripheral blood mononuclear cells from clinical ACLF patients and healthy controls. Integrated analysis was performed to identify the role of B cells in ACLF. Subsequently, different subsets of B cells in ACLF were validated through flow cytometry based on their highlighted markers. Six B‐cell subgroups, including naive B cells, naive B2 cells, nonclass‐switched memory B cells, class‐switched memory B cells, autoimmune‐related B cells and plasma B cells were identified. The proportions of naive B cells significantly expand in ACLF, compared with healthy control. Function enrichment analysis revealed the activation of inflammatory response in naive B cells. Further flow cytometry confirmed the elevated circulating naive B cells in ACLF. Our study uncovered the altered immune landscape of circulating B cells after ACLF. The proportion dynamics and functional perturbation indicate the potential of naive B cells as intervention targets in the future ACLF therapy.