Helicobacter-stimulated IL-10-producing B cells suppress differentiation of lipopolysaccharide/Helicobacter felis-activated stimulatory dendritic cells

Authors: DOĞUŞ ALTUNÖZ, AYÇA SAYI YAZGAN

Abstract: Regulatory B cells (Bregs) produce antiinflammatory cytokines and inhibits proinflammatory response. Recently, immunosuppressive roles of Bregs in the effector functions of dendritic cells (DCs) were demonstrated. However, cross talk between Bregs and DCs in Helicobacter infection remains unknown. Here, we showed that direct stimulation of bone marrow-derived DCs (BMDCs) with Helicobacter felis (H. felis) antigen upregulates their CD86 surface expression and causes the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and interleukin-10 (IL-10). Furthermore, prestimulation of DCs with supernatants derived from both Helicobacter-stimulated IL-10^- B (Hf_stim-IL-10^- B) or IL-10⁺ B (Hf_stim-IL-10⁺) cells suppresses the secretion of TNF-α and IL-6, but does not affect the expression of CD86 and secretion of IL-12 by lipopolysaccharide (LPS) or H. felisactivated BM-DCs. Remarkably, soluble factors secreted by Hf_stim-IL-10^- B cells, but not by Hf_stim-IL-10⁺ B cells, suppress the secretion of IL-10 by BM-DCs upon subsequent LPS stimulation. In contrast, prestimulation with BM-DCs with supernatants of Hf_stim-IL-10⁺ B cells before H. felis antigen stimulation induces significantly their IL-10 production. Collectively, our data indicated that prestimulation with soluble factors secreted by Hf_stim-IL-10⁺ B cells, DCs exhibit a tolerogenic phenotype in response to LPS or Helicobacter antigen by secreting high levels of IL-10, but decreased levels of IL-6 and TNF-α.

Keywords: Helicobacter felis, regulatory B cells, dendritic cells, lipopolysaccharide

Full Text: PDF