Characteristics of regulatory B cells in patients with chronic hepatitis B virus infection in different immune phases.

Regulatory B cells (Bregs) are reported to play an important role in the immune responses to chronic hepatitis B virus (HBV) via Toll-like-receptors (TLRs) signaling. We aimed to investigate the characteristics of Bregs and the expressions of TLRs in Bregs in the peripheral blood of different immune phases of patients with chronic HBV infection. In this study, we determined the frequencies of Bregs and TLR9, TLR2, and TLR4 in peripheral blood using flow cytometry and determined the levels of IL-10 in serum with the Human Magnetic Cytokine/Chemokine Bead Panel. The results showed that the frequencies of CD19+ B cells and Bregs were elevated in patients with chronic HBV infection compared with healthy control (HC). The frequencies of Bregs were significantly increased in the immune active group compared with the immune tolerant group and HC group. Meanwhile, the frequencies of Bregs were higher in inactive carrier state group compared with HC group. The levels of serum IL-10 were elevated in the immune active group compared with immune tolerant, inactive carrier state and HC groups. Serum IL-10 levels were positively correlated with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the immune active group. Compared with HC group, the expression of TLR9 in Bregs reduced in chronic hepatitis B (CHB) patients. However, the expression of TLR2 in Bregs increased in CHB patients. There were no differences of the TLRs expressions in Bregs among various immune phases of chronic HBV infection. These data suggest that the frequencies of Bregs and levels of serum IL-10 were different in various immune phases in patients with chronic HBV infection. Bregs may play some important role in modulating the immune responses of chronic HBV infection. However, whether Bregs modulate immune responses via TLR signaling in chronic HBV infection remains ambiguous.