Circulating regulatory Tfh cells are enriched in patients with chronic hepatitis B infection and induce the differentiation of regulatory B cells.

Chronic hepatitis B virus (HBV) infection is a complex disease with dysregulations in the immune system. Follicular helper T (Tfh) cells are professional B helper cells that are crucial to the development of antibody responses and are involved in a variety of diseases. In this study, we examined the circulating Tfh cells in patients with chronic HBV infection. We observed that CD3+CD4+CXCR5+ circulating Tfh cells contained a CD25+Foxp3+ Treg-like subset that was significantly enriched in patients with chronic HBV infections. The CD25+ Tfh subset presented distinctive cytokine secretion profile, such as lower interferon (IFN)-γ and interleukin (IL)-17, and higher transforming growth factor (TGF)-β secretion, compared to the CD25- Tfh subset. When incubated with autologous naive CD10-CD27-CD19+ B cells, the CD25+ Tfh subset was less capable of mediating CD20-/loCD38+ plasmablast differentiation than the CD25- Tfh subset. In terms of Ig production, CD25+ Tfh cells were more potent at inducing IgM but less potent at inducing IgG and IgA than CD25- Tfh cells. Interestingly, B cells following incubation with CD25+ Tfh cells presented elevated regulatory function, with higher production of IL-10 and enhanced capacity of suppressing autologous CD8+ T cell inflammation. In the chronic HBV-infected patients, the frequency of IL-10+ B cells and the HBV viral load were positively correlated with the frequency of CD25+Foxp3+ CD4+CXCR5+ Tfh cells. Together, this study presented that CD25+Foxp3+ Treg-like Tfh cells were enriched in chronic HBV-infected patients and could promote regulatory B cell functions.