CD19(+)CD24(hi)CD38(hi)Bregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer

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(+)CD24(hi)CD38(hi) 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(+)CD24(hi)CD38(hi)Bregs 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.