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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 (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 (Hfstim-IL-10– B) or IL-10+ B (Hfstim-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. | Turkish Journal of Biology Turk J Biol 2021 45 214-224 http journals.tubitak.gov.tr biology TÜBİTAK Research Article doi 10.3906 biy-2012-11 Helicobacter-stimulated IL-10-producing B cells suppress differentiation of lipopolysaccharide Helicobacter felis-activated stimulatory dendritic cells Doğuş ALTUNÖZ Ayça SAYI YAZGAN Department of Molecular Biology and Genetics Faculty of Science and Letters İstanbul Technical University İstanbul Turkey Received 04.12.2020 Accepted Published Online 24.03.2021 Final Version 20.04.2021 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 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 Hfstim-IL-10 B or IL-10 B Hfstim-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 Hfstim-IL-10 B cells but not by Hfstim-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 Hfstim-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 Hfstim-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 .