| First Author | Sayi A | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 2 | Pages | 878-90 |
| PubMed ID | 21149607 | Mgi Jnum | J:168773 |
| Mgi Id | MGI:4938219 | Doi | 10.4049/jimmunol.1002269 |
| Citation | Sayi A, et al. (2011) TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells. J Immunol 186(2):878-90 |
| abstractText | 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. |
