International Immunology, Vol. 13, No. 9, 1155-1163,
September 2001
© 2001 Japanese Society for Immunology
Murine models of systemic lupus erythematosus: B and T cell responses to spliceosomal ribonucleoproteins in MRL/Faslpr and (NZB x NZW)F1 lupus mice
Institut de Biologie Moléculaire et Cellulaire, UPR 9021 Centre National de la Recherche Scientifique, 15 rue René Descartes, 6700 Strasbourg, France
1 Division of Rheumatology, Department of Internal Medicine III, and Institute of Medical Biochemistry, University of Vienna, Dr Bohr-Gasse 9, A-1030 Vienna, Austria
2 Present address: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
Correspondence to: S. Muller
(NZB x NZW)F1 and MRL/Faslpr lupus mice present a similar phenotype with a spectrum of autoantibodies associated with very severe nephritis. It is thought, however, that in contrast to other lupus-prone mice such as MRL/Faslpr mice, (NZB x NZW)F1 mice do not generate autoantibodies to ribonucleoproteins (RNP) Sm/RNP. In this study, we demonstrate that contrary to previous reports, the autoimmune response directed against Sm/RNP antigens also occurs in NZB x NZW mice. CD4+ T cells from unprimed 10-week-old NZB x NZW mice proliferate and secrete IL-2 in response to peptide 131–151 of the U1-70K protein, which is known to contain a Th epitope recognized by CD4+ T cells from MRL/Faslpr mice. Peptide 131–151, which was found to bind I-Ak and I-Ek class II MHC molecules, also bound both I-Ad and I-Ed molecules. This result led us to also re-evaluate longitudinally the anti-Sm/RNP antibody response in NZB x NZW mice. We found that 25-week-old mice do produce antibodies reacting with several small nuclear and heterogeneous nuclear (hn) RNP proteins, such as SmD1, U1-70K and hnRNP A2/B1 proteins. The fine specificity of these antibodies was studied with overlapping synthetic peptides. The same antigenically positive and negative peptides were characterized in MRL/Faslpr and NZB x NZW mice in the three proteins. This new finding can help to understand the mechanisms involved in the development of the anti-Sm/RNP antibody response and, particularly, the role played by non-MHC genes in this autoimmune response.
Keywords: autoimmunity, epitopes, lupus animal models, T lymphocytes
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