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*
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
University of North Carolina School of Medicine, Chapel Hill, NC 27599;
Department of Surgery, University of Wisconsin Medical School, Madison, WI 53706;
§
Department of Comparative Medicine, University of Tennessee, Knoxville, TN 37901; and
¶
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262
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 
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.
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