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 CD3CD4CXCR5 circulating Tfh cells contained a CD25Foxp3 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 CD10CD27CD19 B cells, the CD25 Tfh subset was less capable of mediating CD20CD38 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 CD25Foxp3 CD4CXCR5 Tfh cells. Together, this study presented that CD25Foxp3 Treg-like Tfh cells were enriched in chronic HBV-infected patients and could promote regulatory B cell functions.