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

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 (BM-DCs) 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. felis-activated 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.