Intrahepatic plasma cells, but not atypical memory B cells, associate with clinical phases of chronic hepatitis B

Studies have traditionally focused on the role of T cells in chronic hepatitis B (CHB), but recent evidence supports a role for B cells. The enrichment of so‐called atypical memory (AtM) B cells, which show reduced signaling and impaired differentiation, is believed to be a characteristic feature of CHB, potentially contributing to the observed dysfunctional anti‐HBsAg B‐cell responses. Our study, involving 62 CHB patients across clinical phases, identified AtM B cells expressing IFNLR1 and interferon‐stimulated genes. Contrary to previous reports, we found relatively low frequencies of AtM B cells in the liver, comparable to peripheral blood. However, liver plasma cell frequencies were significantly higher, particularly during phases with elevated viral loads and liver enzyme levels. Liver plasma cells exhibited signs of active proliferation, especially in the immune active phase. Our findings suggest a potential role for plasma cells, alongside potential implications and consequences of local proliferation, within the livers of CHB patients. While the significance of AtM B cells remains uncertain, further investigation is warranted to determine their responsiveness to interferons and their role in CHB. Our study explored B‐cell subsets in the blood and liver of chronic hepatitis B patients using single‐cell sequencing. Here we found relatively low frequencies of atypical memory B cells in both the blood and liver, whereas a significantly higher frequency of plasma cells was found in liver samples; particularly during active clinical phases.