title: Discerning the kinetics of autoimmune manifestations in a model of Sjögren's syndrome.
abstract: Ectopic follicles are non-encapsulated organized lymphoid structures that form at sites of inflammation and presumably contribute to the activation and differentiation of cells with autoreactive potential within target tissues. As such, directed targeting of ectopic follicles in settings of autoimmunity may provide a means to specifically inhibit the activation of autoreactive cells without impairing protective immune responses ongoing in peripheral lymphoid tissues. NOD·H2h4 mice are a non-diabetic strain of NOD mice which develop a Sjögren's syndrome-like disease which includes the formation of ectopic follicles in the salivary gland and characteristic Sjögren's autoantibodies. The goal of these studies was to better characterize the formation of ectopic follicles in this model and to explore their contribution to autoimmunity. Our studies show that by 8 weeks of age, young NOD·H2h4 mice spontaneously develop an abundance of splenic germinal centers, prior to the emergence of lymphocyte infiltration in the salivary gland tissue. Ectopic follicle formation in the salivary gland begins to appear in these mice between 12 and 16 weeks of age. Interestingly, anti-Ro and anti-La autoantibodies precede the development of ectopic follicles in young NOD·H2h4 mice. In contrast, production of anti-dsDNA antibodies is delayed and largely coincides with the formation of ectopic follicles in these mice. These data suggest that tertiary lymphoid structures may arise from the trafficking of activated T and B cells to sites of inflammation in non-lymphoid tissues. Furthermore, local presentation of autoantigens may then promote the expansion of autoreactive cells with specificities distinct from those generated in the splenic micro-environment.
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, MD 20878, United States.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Karnell
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, MD 20878, United States.
authors.forename: Tamer I
authors.initials: TI
authors.lastname: Mahmoud
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, MD 20878, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: MedImmune, One MedImmune Way, Gaithersburg, MD 20878, United States. Electronic address: ettingerc@medimmune.com.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018858:Germinal Center / Q000276:immunology; D007700:Kinetics; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D012469:Salivary Glands / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens
keywords: Autoantibody; B cell; Ectopic follicle; Sjögren's syndrome