title: Periodontitis in the absence of B cells and specific anti-bacterial antibody.
abstract: Periodontitis (PD) results from complex interactions between a dysbiotic oral microbiota and a dysregulated host immune response. The inflammatory infiltrate in the gingiva of PD patients includes an abundance of B cells, implicating these cells in the immunopathology. We sought to investigate the role of B cells in PD using a murine model. Wild-type or B-cell-deficient (μMT) mice were orally infected with Porphyromonas gingivalis. One or six weeks following infection, lymphocyte populations in the gingiva and cervical draining lymph nodes (dLN) were analysed by flow cytometry; serum anti-P. gingivalis IgG antibody titers were measured by enzyme-linked immunosorbent assay, and alveolar bone loss was determined. In wild-type mice, the percentage of gingival B cells expressing receptor activator of nuclear factor-κB ligand (RANKL) was significantly increased 1 week post-infection (5.36% control versus 11% PD, P < 0.01). The percentage of Fas(+) GL7(+) germinal centre B cells in the dLN was significantly increased at both 1 week (2.03% control versus 6.90% PD, P < 0.01) and 6 weeks (4.45% control versus 8.77% PD, P < 0.05) post-infection. B-cell-deficient mice were protected from P. gingivalis-induced alveolar bone loss, with a lack of B-cell proliferation and lack of CD4(+) CD44(+) CD62L(-) T-cell generation in the dLN, and absence of serum anti-P. gingivalis antibodies. Our data imply a pathological role for B cells in PD, and that selective targeting of this immune axis may have a role in treating severe periodontal disease.
authors.affiliation: Institute of Infection Immunology and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Oliver-Bell
authors.forename: J P
authors.initials: JP
authors.lastname: Butcher
authors.forename: J
authors.initials: J
authors.lastname: Malcolm
authors.forename: M K L
authors.initials: MK
authors.lastname: MacLeod
authors.forename: A
authors.initials: A
authors.lastname: Adrados Planell
authors.forename: L
authors.initials: L
authors.lastname: Campbell
authors.forename: R J B
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: P
authors.initials: P
authors.lastname: Garside
authors.forename: I B
authors.initials: IB
authors.lastname: McInnes
authors.forename: S
authors.initials: S
authors.lastname: Culshaw
mesh_terms: D016301:Alveolar Bone Loss / Q000382:microbiology / Q000473:pathology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005881:Gingiva / Q000382:microbiology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse
keywords: B cells; murine models; periodontitis