title: A critical role for lymphotoxin-beta receptor in the development of diabetes in nonobese diabetic mice.
abstract: To assess the role of lymphotoxin-beta receptor (LTbetaR) in diabetes pathogenesis, we expressed an LTbetaR-Fc fusion protein in nonobese diabetic (NOD) mice. The fusion protein was expressed in the embryo, reached high levels for the first 2 wk after birth, and then declined progressively with age. High expression of LTbetaR-Fc blocked diabetes development but not insulitis. After the decline in chimeric protein concentration, mice became diabetic with kinetics similar to the controls. Early expression of fusion protein resulted in disrupted splenic architecture. However, primary follicles and follicular dendritic cells, but not marginal zones, developed in aged mice. Hence, LTbetaR signaling is required for diabetes development and regulates follicular and marginal zone structures via qualitatively or quantitatively distinct mechanisms.
authors.affiliation: Basel Institute for Immunology, Basel CH-4005, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Ettinger
authors.forename: S H
authors.initials: SH
authors.lastname: Munson
authors.forename: C C
authors.initials: CC
authors.lastname: Chao
authors.forename: M
authors.initials: M
authors.lastname: Vadeboncoeur
authors.forename: J
authors.initials: J
authors.lastname: Toma
authors.forename: H O
authors.initials: HO
authors.lastname: McDevitt
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D018858:Germinal Center / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000276:immunology; D007515:Islets of Langerhans / Q000473:pathology; D053259:Lymphotoxin beta Receptor; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*
chemical_list: C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D005968:Glutamate Decarboxylase