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Selective pathogenicity of murine rheumatoid factors of the cryoprecipitable IgG3 subclass

Berney, Thierry ; Fulpius, Thierry ; Shibata, Takanori ; Reininger, Luc ; Van Snick, Jacques ; Shan, Hua ; Weigert, Martin ; Marshak-Rothstein, Ann ; Izui, Shozo

In: International Immunology, 1992, vol. 4, no. 1, p. 93-99

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    Titre
    • Selective pathogenicity of murine rheumatoid factors of the cryoprecipitable IgG3 subclass
    Auteur
    • Berney, Thierry. Department of Pathology, Centre Médical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland, Brussels, Belgium, Philadelphia, PA 19111, USA, Boston, MA 02118, USA
    • Fulpius, Thierry. Department of Pathology, Centre Médical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland, Brussels, Belgium, Philadelphia, PA 19111, USA, Boston, MA 02118, USA
    • Shibata, Takanori. Department of Pathology, Centre Médical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland, Brussels, Belgium, Philadelphia, PA 19111, USA, Boston, MA 02118, USA
    • Reininger, Luc. Department of Pathology, Centre Médical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland, Brussels, Belgium, Philadelphia, PA 19111, USA, Boston, MA 02118, USA
    • Van Snick, Jacques. Ludwing Institute for Cancer Research Brussels, Belgium
    • Shan, Hua. Institute for Cancer Research, Fox Chase Cancer Center Philadelphia, PA 19111, USA
    • Weigert, Martin. Institute for Cancer Research, Fox Chase Cancer Center Philadelphia, PA 19111, USA
    • Marshak-Rothstein, Ann. Department of Microbiology, Boston University Medical Center Boston, MA 02118, USA
    • Izui, Shozo. Department of Pathology, Centre Médical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland, Brussels, Belgium, Philadelphia, PA 19111, USA, Boston, MA 02118, USA
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • International Immunology, 1992, vol. 4, no. 1, p. 93-99. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:302686
    Summary
    To analyze the involvement of rheumatoid factors (RF) in the generation of cryoglobulins and the development of related tissue injuries, we have established a panel of anti-IgG2a RF mAbs derived from MRL/MpJ-lpr/lpr (MRL-lpr), C3H/HeJ-lpr/lpr, and 129/Sv mice. After injection of hybridoma cells to normal mice, all four IgG3 RF mAbs induced cryoglobullnemia, and various degrees of glomerulonephritis and skin leukocytoclastic vasculitis. In contrast, none of the RF mAbs of the other isotypes generated cryoglobulins or tissue lesions. Since the same observation was obtained with another panel of five clonally related anti-IgG2a RF mAbs of MRL-lpr origin with almost Identical heavy and light chain variable (V) regions but five different Isotypes, it seems unlikely that the absence of pathogenicity of non-IgG3 RF mAbs was due to differences in fine specificity or V framework regions. In addition, the analysis of serum RF In MRL-lpr mice has demonstrated that a majority of 4 month old MRL-lpr mice produced substantial amounts of IgG3 RF with cryoglobulin activity. Because the cryoglobulin activity is associated with the murine IgG3 heavy chain constant region, RF of this subclass may play a significant role in the development of autoimmune-related tissue injuries, especially In MRL-lpr mice