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CXCR5 BACKGROUND AND AIM: Hepatitis B-associated liver cirrhosis (HBC) leads to profound alterations of immune systems, especially disruptions of B cell immune responses. CXCR5+ CD4+ T cells (including T follicular helper [Tfh] cells and T follicular regulatory [Tfr] cells) are responsible for the regulation of B cell functions. The aim of this study was to dissect the roles of CXCR5+ CD4+ T cell subset in B cell disruption caused by HBC. METHODS: Forty-one patients with HBC and 15 healthy controls were enrolled in this study. ELISA, flow cytometric analysis, and cell coculture were performed to analyze the properties of Tfh and Tfr. RESULTS: We observed significantly decreased memory B cells and increased plasma B cells in HBC patients, as well as significant upregulation of lipopolysaccharide binding protein and soluble CD14 in plasma of decompensated HBCs patients. The downregulation of Tfh17 was observed in HBC patients with spontaneous bacterial peritonitis compared with those without. The decrease of Tfh17 was paralleled with Child-Pugh grade and negatively correlated with plasma B cells and soluble CD14 in HBC patients. Interleukin (IL)-21+ Tfh of HBC patients was also downregulated compared with healthy controls, and it was positively correlated with memory B cells and the upregulation of IL-10+ Tfr. It was then revealed that Tfr could inhibit the secretion of IL-21 by Tfh, and the blocking of IL-10 could diminish this effect. CONCLUSIONS: The changes of the frequency and function of Tfh and Tfr may play an important role in disease progression and immune dysfunction of HBC.