CD72 downregulation is associated with increased CD5+ B cell proliferation and IL-10 production via ERK/Syk signaling in chronic HBV infection-associated liver disease.

Chronic hepatitis B virus (HBV) infection is characterized by selective impairment of virus-specific immune responses. However, progressive liver disease, particularly cirrhosis, is associated with broader immune remodeling that may influence B cell phenotype and function. CD72 is a negative regulator of B cell receptor (BCR) signaling but its role in CD5+B cell regulation under these conditions remains unclear. Peripheral Blood Mononuclear cells (PBMCs) were isolated from 51 HBV-infected patients at differing disease stages and 24 healthy controls by density gradient centrifugation. B cells were isolated using CD19 microbeads. CD72 expression, B cell proliferation, protein phosphorylation and cytokine secretion were assessed by flow cytometry, BrdU assay, Western blotting, lentiviral shRNA-mediated knockdown, RT-qPCR and ELISA. CD72 expression significantly decreased in HBV patient CD5+ B cells but increased in CD5- B cells, correlating negatively with CD5 expression. CD72 knockdown enhanced CD5+ B cell proliferation 2.1-fold (P < 0.01) and increased IL-10, IL-6 and IgM secretion. This phenotype depended on ERK/Syk activation, evidenced by elevated p-ERK levels and abolished proliferation upon ERK/Syk inhibition (P < 0.001). No effects were observed in CD5- B cells. CD72 downregulation enhanced the activation and regulatory function of CD5+B cells through ERK/Syk signaling under conditions associated with chronic liver disease. These findings suggest that alterations in CD72 expression may contribute to B cell functional remodeling in the context of HBV-related liver pathology.