The role of environmental antigens in the spontaneous development of autoimmunity in MRU-lpr mice

It has been proposed that the "normal" stimulation of the immune system tha t occurs from interactions with environmental stimuli, whether infectious o r dietary, is necessary for the initiation and/or continuation of autoimmun ity. We tested this hypothesis by deriving a group of MRL-lpr mice into a g ermfree (GF) environment. At 5 mo of age, no differences between GF and con ventional MRL-lpr mice were noted in lymphoproliferation, flow cytometric a nalysis of lymph node cells (LN), or histologic analysis of the kidneys, Au toantibody levels were comparably elevated in:both groups. A second experim ent tested the role of residual environmental stimuli by contrasting GF mic e fed either a low m.w., ultrafiltered Ag-free (GF-AF) diet or an autoclave d natural ingredient diet (GF-NI), At 4 mo of age, both groups showed exten sive lymphoproliferation and aberrant T cell formation, although the GF-AF: mice had similar to 50% smaller LNs compared with sex-matched F-M controls, Autoantibody formation was present in both groups. Histologic analysis of the kidneys revealed that GF-AF mice had much lower levels of nephritis, wh ile immunofluorescence analysis demonstrated no difference in Ig deposits b ut-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 MRC-lpr mice. Furthermore, t hey suggest that autoantibodies db hot originate from B cells that were ini tially committed to exogenous Ags, They do suggest a possible contributory role for dietary exposure in the extent of lymphoproliferation and developm ent of nephritis in this strain.