IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection

Abstract

Non-specific immune responses to antigens have been demonstrated as being enhanced during chronic hepatitis B virus (HBV) infection. Here, we evaluated the role of interleukin-10 (IL-10)-producing regulatory B-cells (Bregs) in the pathogenesis of HBV-related liver fibrosis (HBV-LF) and assessed their immunoregulatory effects. Sixty-seven patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. Numbers and frequencies of peripheral B-cells (memory CD19(+)CD24(hi)CD27(+) cells, immature/transitional CD19(+)CD24(hi)CD38(hi) cells, mature CD19(+)CD24(int)CD38(int) cells) were tested and analysed. Flow cytometry-sorted CD4(+)T cells were cultured with autologous Bregs to elucidate the effects of Bregs on CD4(+)T cells, including effector T and regulatory T-cells (Tregs). The potential immunoregulatory mechanism of Bregs was also investigated. The numbers of total B-cells and Bregs were enriched in CHB patients. The frequency of Bregs was negatively correlated with elevated alanine aminotransferase (ALT) and histological inflammation grades (G), but positively correlated with advanced histological fibrosis stages (S) and enhanced HBV replication. The phenotype of Bregs was predominantly characterized as CD19(+)CD24(hi)CD38(hi) In co-culture with Bregs, CD4(+)CD25(-)T cells from CHB patients produced less interferon-γ (IFN-γ) and IL-17 but more IL-4 than CD4(+)CD25(-)T cells alone, whereas their conversions into Tregs and IL-10(+)T cells were enhanced. In addition, Breg depletion in CHB samples dramatically decreased Treg numbers and expression of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), IL-10 and transforming growth factor-β (TGF-β). Moreover, the observed regulatory effect was partly dependent on IL-10 release and cell-to-cell contact. Elevated Bregs can suppress effector T but enhance Treg functions, which might influence immune tolerance in chronic HBV infection.

Regulatory B cells induced by ultraviolet B through toll‐like receptor 4 signalling contribute to the suppression of contact hypersensitivity responses in mice

“…Liu et al. observed that, in chronic hepatitis B virus infection, regulatory B cells could enhance regulatory T cell function and influence immune tolerance . Whether regulatory T cells and regulatory B cells underwent synergistic interactions in maintaining UVB‐induced immunosuppression was still undetermined in our study.…”

“…However, because of the lack of regulatory T cell depletion experiments in our study, we cannot exclude a suppressive role of regulatory T cells in our research model. Sun immune tolerance (36). Whether regulatory T cells and regulatory B cells underwent synergistic interactions in maintaining UVB-induced immunosuppression was still undetermined in our study.…”

Changes in Regulatory T-Cell Levels in Acute Cerebral Ischemia

“…Treg cells could release CTLA-4, IL-10, and other immune mediators/molecules to resist the invasion of Teff and antigen-presenting cells to modulate the local microenvironment. 34 However, the function of Treg cells in acute infections has not been elucidated. Some scientists found that patients infected with influenza A virus might have an accumulation of Treg cells.…”

B‐cell‐specific‐peroxisome proliferator‐activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells

“…a,b). The Breg cells can induce Foxp3 + Treg cells to perform inhibitory functions . Therefore, we examined the CD4 + CD25 + Foxp3 + Treg cell frequencies in peripheral blood of naive B‐PPAR‐ γ −/− mice and control mice (Fig.…”

“…This finding was in line with the previous report that loss of PPAR‐ γ in B cells did not affect the development of B cells or B‐cell populations, such as pro‐B cells, pre‐B cells, follicular B cells, marginal zone precursor cells, marginal zone cells, among others, in spleen or bone marrow . As reported, mice lacking Breg cells presented with reduced Treg cell frequency . We next investigated the CD4 + CD25 + Foxp3 + Treg cells in peripheral blood and observed no significant change in B‐PPAR‐ γ −/− mice.…”