Immunoglobulin heavy chain constant region determines the pathogenicity and the antigen-binding activity of rheumatoid factor

Détails

ID Serval
serval:BIB_6DD2DDED1DC6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Immunoglobulin heavy chain constant region determines the pathogenicity and the antigen-binding activity of rheumatoid factor
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
Fulpius  T., Spertini  F., Reininger  L., Izui  S.
ISSN
0027-8424 (Print)
Statut éditorial
Publié
Date de publication
03/1993
Volume
90
Numéro
6
Pages
2345-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Résumé
An IgG3 monoclonal antibody, 6-19, derived from unmanipulated MRL/MpJ-lpr/lpr mice, exhibiting cryoglobulin and anti-IgG2a rheumatoid factor activities, induces skin leukocytoclastic vasculitis and glomerulonephritis when injected into normal mice. To determine the role of the gamma 3 heavy chain constant region in the generation of cryoglobulins and associated tissue lesions, we have established an IgG1 class switch variant, clone SS2F8, from the 6-19 hybridoma by sequential sublining. Here we report that the SS2F8 monoclonal antibody, which loses the cryoglobulin activity but retains the rheumatoid factor activity, fails to generate skin and glomerular lesions. The lack of pathogenicity of the IgG1 SS2F8 switch variant is not due to mutations in variable regions, since nucleotide sequence analysis shows no differences between both clones. In addition, we have observed that the IgG1 SS2F8 switch variant exhibits < 10% of the rheumatoid factor activity, as compared with the IgG3 6-19 monoclonal antibody, suggesting that the self-associating property of the gamma 3 isotype promotes antibody-binding activity. The present study indicates that the cryoglobulin activity associated with the gamma 3 isotype is critically involved in the pathogenicity of 6-19 anti-IgG2a rheumatoid factor monoclonal antibody and highlights the pathogenic relevance of autoantibodies of the IgG3 subclass in murine systemic lupus erythematosus.
Mots-clé
Animals Antibodies, Monoclonal/*immunology/toxicity Base Sequence Cloning, Molecular Crosses, Genetic Cryoglobulins/biosynthesis Enzyme-Linked Immunosorbent Assay Female Glomerulonephritis/*immunology/pathology Immunoglobulin Constant Regions/*immunology/toxicity Immunoglobulin Fab Fragments/immunology/toxicity Immunoglobulin G/classification/*immunology/toxicity Immunoglobulin Heavy Chains/*immunology/toxicity Kidney/immunology/pathology Male Mice Mice, Inbred BALB C Mice, Inbred Strains Molecular Sequence Data Oligodeoxyribonucleotides Polymerase Chain Reaction Rheumatoid Factor/*immunology Skin/*immunology/pathology Vasculitis, Allergic Cutaneous/*immunology/pathology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:19
Dernière modification de la notice
20/08/2019 14:27
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