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

Michael A. Maldonado, Vellalore Kakkanaiah, Glen C. MacDonald, Fangqi Chen, Elizabeth A. Reap, Edward Balish, Walter R. Farkas, J. Charles Jennette, Michael P. Madaio, Brian L. Kotzin, Philip L. Cohen, Robert A. Eisenberg

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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 ~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.

Original languageEnglish (US)
Pages (from-to)6322-6330
Number of pages9
JournalJournal of Immunology
Volume162
Issue number11
StatePublished - Jun 1 1999

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Inbred MRL lpr Mouse
Autoimmunity
Autoantibodies
Antigens
Nephritis
Kidney
B-Lymphocytes
Diet
Fluorescent Antibody Technique
Immune System
Age Groups
Lymph Nodes
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Maldonado, M. A., Kakkanaiah, V., MacDonald, G. C., Chen, F., Reap, E. A., Balish, E., ... Eisenberg, R. A. (1999). The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. Journal of Immunology, 162(11), 6322-6330.

The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. / Maldonado, Michael A.; Kakkanaiah, Vellalore; MacDonald, Glen C.; Chen, Fangqi; Reap, Elizabeth A.; Balish, Edward; Farkas, Walter R.; Jennette, J. Charles; Madaio, Michael P.; Kotzin, Brian L.; Cohen, Philip L.; Eisenberg, Robert A.

In: Journal of Immunology, Vol. 162, No. 11, 01.06.1999, p. 6322-6330.

Research output: Contribution to journalArticle

Maldonado, MA, Kakkanaiah, V, MacDonald, GC, Chen, F, Reap, EA, Balish, E, Farkas, WR, Jennette, JC, Madaio, MP, Kotzin, BL, Cohen, PL & Eisenberg, RA 1999, 'The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice', Journal of Immunology, vol. 162, no. 11, pp. 6322-6330.
Maldonado MA, Kakkanaiah V, MacDonald GC, Chen F, Reap EA, Balish E et al. The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. Journal of Immunology. 1999 Jun 1;162(11):6322-6330.
Maldonado, Michael A. ; Kakkanaiah, Vellalore ; MacDonald, Glen C. ; Chen, Fangqi ; Reap, Elizabeth A. ; Balish, Edward ; Farkas, Walter R. ; Jennette, J. Charles ; Madaio, Michael P. ; Kotzin, Brian L. ; Cohen, Philip L. ; Eisenberg, Robert A. / The role of environmental antigens in the spontaneous development of autoimmunity in MRL-lpr mice. In: Journal of Immunology. 1999 ; Vol. 162, No. 11. pp. 6322-6330.
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AU - Reap, Elizabeth A.

AU - Balish, Edward

AU - Farkas, Walter R.

AU - Jennette, J. Charles

AU - Madaio, Michael P.

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AU - Cohen, Philip L.

AU - Eisenberg, Robert A.

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