title: Production of autoantibodies by murine B-1a cells stimulated with Helicobacter pylori urease through toll-like receptor 2 signaling.
abstract: Helicobacter pylori infection is associated with several autoimmune diseases, in which autoantibody-producing B cells must be activated. Among these B cells, CD5-positive B-1a cells from BALB/c mice were confirmed to secrete autoantibodies when cocultured with purified H. pylori urease in the absence of T cells. To determine the mechanisms for autoantibody production, CD5-positive B-1a cells were sorted from murine spleen cells and stimulated with either purified H. pylori urease or H. pylori coated onto plates (referred to hereafter as plate-coated H. pylori), and autoantibody production was measured by enzyme-linked immunosorbent assay (ELISA). Complete urease was not secreted from H. pylori but was visually expressed over the bacterium-like endotoxin. Urease-positive plated-coated H. pylori stimulated B-1a cells to produce autoantibodies, although urease-deficient isotype-matched H. pylori did not. Autoantibody secretion by B-1a cells was inhibited when bacteria were pretreated with anti-H. pylori urease-specific antibody having neutralizing ability against urease enzymatic activity but not with anti-H. pylori urease-specific antibody without neutralizing capacity. The B-1a cells externally express various Toll-like receptors (TLRs): TLR1, TLR2, TLR4, and TLR6. Among the TLRs, blocking of TLR2 on B-1a cells with a specific monoclonal antibody (MAb), T2.5, inhibited autoantibody secretion when B-1a cells were stimulated with plate-coated H. pylori or H. pylori urease. Moreover, B-1a cells from TLR2-knockout mice did not produce those autoantibodies. The present study provides evidence that functional urease expressed on the surface of H. pylori will directly stimulate B-1a cells via innate TLR2 to produce various autoantibodies and may induce autoimmune disorders.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kobayashi
authors.forename: Eri
authors.initials: E
authors.lastname: Watanabe
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamanishi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Norose
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D016480:Helicobacter pylori / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014510:Urease / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014510:Urease