CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer

Abstract

Regulatory B cells (Bregs) play a critical role in inflammation and autoimmune disease. We characterized the role of Bregs in the progression of gastric cancer. We detected an increase in Bregs producing IL-10 both in peripheral blood mononuclear cells (PBMCs) and in gastric tumors. Multicolor flow cytometry analysis revealed that a subset of CD19+CD24hiCD38hi B cells produces IL-10. Functional studies indicated that increased Bregs do not inhibit the proliferation of CD3+T cells or CD4+ helper T cells (Th cells). However, Bregs do suppress the secretion of IFN-γ and TNF-α by CD4+Th cells. CD19+CD24hiCD38hiBregs were also found to correlate positively with CD4+FoxP3+ regulatory T cells (Tregs). Neutralization experiments showed that Bregs convert CD4+CD25− effector T cells to CD4+FoxP3+Tregs via TGF-β1. Collectively, these findings demonstrate that increased Bregs play a immunosuppressive role in gastric cancer by inhibiting T cells cytokines as well as conversion to Tregs. These results may provide new clues about the underlying mechanisms of immune escape in gastric cancer.

IFN‐γ stimulates CpG‐induced IL‐10 production in B cells via p38 and JNK signalling pathways

“…In human PBMCs, we identified naïve B cells (CD19 + CD27 − ) and to a lesser extent transitional (CD19 + CD24 hi CD38 hi ) and memory B cells (CD19 + CD27 + ) as IL‐10‐producing target cells for CpG+IFN‐γ stimulation, while plasma B cells (CD19 + CD24 − CD38 hi ) were not responsive. Our results are in line with previous reports, which showed that CD27 − B cells (corresponding to naïve B cells), transitional B cells, CD24 hi CD27 + (overlapping with the phenotype of memory B cells) and CD73 − CD25 + CD71 + B cells can all produce IL‐10 . Apparently, no clearcut phenotypic markers can be used to characterize IL‐10‐producing B cells.…”

The correlation of CD19 + CD24 + CD38 + B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patients

“…FoxP3 ? T cells in a TGF-b dependent way in gastric cancer patients and concluded that CD19 ?-CD24 hi CD38 hi cells involve in gastric cancer immune scape [22]. In our study a significant correlation was found between serum TGF-b and Tregs which suggests that the increase in circulating Tregs may be TGF-b dependent in breast cancer patients.…”

“…effector T cells, including cytokines such as TGF-b and IL-10 [33]. Bregs are also capable of directly inducing anergy of Th1 cells, CD8, and CD4 T cells [34] or indirectly by converting Tregs [19,22]. Some studies indicated that the Tregs immunosuppressive role in tumors is mediated by Bregs [35].…”

“…A recent study also described the role of CD19 ? CD24 hi CD38 hi cells in suppressing tumor immunity in gastric cancer [22].…”

A new perspective: Exploring future therapeutic strategies for cancer by understanding the dual role of B lymphocytes in tumor immunity

“…In gastric cancer, Wang et al . described a subset of Bregs with a phenotype (CD19 + CD24 hi CD38 hi ) conversion of effector T cells into CD4 + FoxP3 + Tregs via TGF‐β1 . However, another study demonstrated that CD19 + CD24 hi CD38 hi B cells of healthy individuals repress the proliferation of CD4 + CD25 − T cells and decrease the production of IFN‐γ and tumor necrosis factor‐α by these cells, in part, by producing IL‐10.…”