title: Salivary glands act as mucosal inductive sites via the formation of ectopic germinal centers after site-restricted MCMV infection.
abstract: We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV-inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4(+) and B220(+) lymphocytes, IgM(+) and isotype-switched IgG(+) and IgA(+) B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin. Lymphoid follicles were characterized by a 2- to 3-fold increase in mRNA for CXCL13 (lymphoid neogenesis), syndecan-1 (plasma cells), Blimp-1 (plasma cell development/differentiation), and a 2- to 6-fold increase for activation-induced cytidine deaminase, PAX5, and the nonexcised rearranged DNA of an IgA class-switch event, supporting somatic hypermutation and class-switch recombination within the salivary follicles. Intraglandular inoculation also provided protection against a systemic MCMV challenge, as evidenced by decreased viral titers (10(5) plaque-forming units to undetectable), and restoration of normal salivary flow rates from a 6-fold decrease. Therefore, these features suggest that the salivary gland participates in oral mucosal immunity via generation of ectopic GCs, which function as ectopic mucosal inductive sites.
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Jasvir S
authors.initials: JS
authors.lastname: Grewal
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pilgrim
authors.forename: Suman
authors.initials: S
authors.lastname: Grewal
authors.forename: Laura
authors.initials: L
authors.lastname: Kasman
authors.forename: Phillip
authors.initials: P
authors.lastname: Werner
authors.forename: Mary E
authors.initials: ME
authors.lastname: Bruorton
authors.forename: Steven D
authors.initials: SD
authors.lastname: London
authors.forename: Lucille
authors.initials: L
authors.lastname: London
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology*; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral