TLR-2–activated B cells suppress helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells

A Sayi, E Kohler, IM Toller, RA Flavell… - The Journal of …, 2011 - journals.aai.org
A Sayi, E Kohler, IM Toller, RA Flavell, W Müller, A Roers, A Müller
The Journal of Immunology, 2011journals.aai.org
B cells regulate autoimmune pathologies and chronic inflammatory conditions such as
autoimmune encephalomyelitis and inflammatory bowel disease. The potential
counterregulatory role of B cells in balancing pathogen-specific immune responses and the
associated immunopathology is less well understood owing to the lack of appropriate
persistent infection models. In this paper, we show that B cells have the ability to negatively
regulate adaptive immune responses to bacterial pathogens. Using mouse models of …
Abstract
B cells regulate autoimmune pathologies and chronic inflammatory conditions such as autoimmune encephalomyelitis and inflammatory bowel disease. The potential counterregulatory role of B cells in balancing pathogen-specific immune responses and the associated immunopathology is less well understood owing to the lack of appropriate persistent infection models. In this paper, we show that B cells have the ability to negatively regulate adaptive immune responses to bacterial pathogens. Using mouse models of infection with Helicobacter felis, a close relative of the human gastrointestinal pathogen H. pylori, we found that B cells activated by Helicobacter TLR-2 ligands induce IL-10–producing CD4+ CD25+ T regulatory-1 (Tr-1)–like cells in vitro and in vivo. Tr-1 conversion depends on TCR signaling and a direct T-/B-interaction through CD40/CD40L and CD80/CD28. B cell-induced Tr-1 cells acquire suppressive activity in vitro and suppress excessive gastric Helicobacter-associated immunopathology in vivo. Adoptive cotransfer of MyD88-proficient B cells and Tr-1 cells restores a normal gastric mucosal architecture in MyD88−/− and IL-10−/− mice in a manner that depends on T cellular, but not B cellular, IL-10 production. Our findings describe a novel mechanism of B cell-dependent Tr-1 cell generation and function in a clinically relevant disease model. In conclusion, we demonstrate that the B cell/Tr-1 cell axis is essential for balancing the control of Helicobacter infection with the prevention of excessive Th1-driven gastric immunopathology, promoting gastric mucosal homeostasis on the one hand and facilitating Helicobacter persistence on the other.
journals.aai.org