title: The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice.
abstract: It has been proposed that the "normal" stimulation of the immune system that occurs from interactions with environmental stimuli, whether infectious or dietary, is necessary for the initiation and/or continuation of autoimmunity. We tested this hypothesis by deriving a group of MRL-lpr mice into a germfree (GF) environment. At 5 mo of age, no differences between GF and conventional MRL-lpr mice were noted in lymphoproliferation, flow cytometric analysis of lymph node cells (LN), or histologic analysis of the kidneys. Autoantibody levels were comparably elevated in both groups. A second experiment tested the role of residual environmental stimuli by contrasting GF mice fed either a low m.w., ultrafiltered Ag-free (GF-AF) diet or an autoclaved natural ingredient diet (GF-NI). At 4 mo of age, both groups showed extensive lymphoproliferation and aberrant T cell formation, although the GF-AF mice had approximately 50% smaller LNs compared with sex-matched GF-NI controls. Autoantibody formation was present in both groups. Histologic analysis of the kidneys revealed that GF-AF mice had much lower levels of nephritis, while immunofluorescence analysis demonstrated no difference in Ig deposits but did reveal a paucity of C3 deposition in the kidneys of GF-AF mice. These data do not support a role for infectious agents in the induction of lymphoproliferation and B cell autoimmunity in MRL-lpr mice. Furthermore, they suggest that autoantibodies do not originate from B cells that were initially committed to exogenous Ags. They do suggest a possible contributory role for dietary exposure in the extent of lymphoproliferation and development of nephritis in this strain.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Maldonado
authors.forename: V
authors.initials: V
authors.lastname: Kakkanaiah
authors.forename: G C
authors.initials: GC
authors.lastname: MacDonald
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: E A
authors.initials: EA
authors.lastname: Reap
authors.forename: E
authors.initials: E
authors.lastname: Balish
authors.forename: W R
authors.initials: WR
authors.lastname: Farkas
authors.forename: J C
authors.initials: JC
authors.lastname: Jennette
authors.forename: M P
authors.initials: MP
authors.lastname: Madaio
authors.forename: B L
authors.initials: BL
authors.lastname: Kotzin
authors.forename: P L
authors.initials: PL
authors.lastname: Cohen
authors.forename: R A
authors.initials: RA
authors.lastname: Eisenberg
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000502:physiology*; D000942:Antigens, Bacterial / Q000502:physiology; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D004032:Diet; D004780:Environment, Controlled; D005260:Female; D005856:Germ-Free Life / Q000276:immunology*; D006799:Housing, Animal; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D009393:Nephritis / Q000209:etiology / Q000276:immunology
chemical_list: D000941:Antigens; D000942:Antigens, Bacterial; D001323:Autoantibodies