Level of galactosylation determines cryoglobulin activity of murine IgG3 monoclonal rheumatoid factor
| Autor: | Thierry Fulpius, Aki Kuroki, Liliane Fossati-Jimack, Munehiro Nakata, Frédéric Lajaunias, Shozo Izui, Yasuhiro Kuroda, Toho Toda, Naoya Kojima, Shuichi Kikuchi, Yves D. Pastore, Tsuguo Mizuochi, Luc Reininger |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Glycosylation
medicine.drug_class Immunoglobulin G/chemistry/genetics/metabolism Immunology Immunoglobulin Variable Region Mice Transgenic ddc:616.07 Monoclonal antibody Biochemistry Antibodies Monoclonal/chemistry/genetics chemistry.chemical_compound Mice Cryoglobulin Rheumatoid Factor Cryoglobulins/ chemistry/genetics medicine Rheumatoid factor Animals Chemical Precipitation Immunoglobulin Heavy Chains/genetics Transgenes Cryoglobulins Immunoglobulin Variable Region/genetics chemistry.chemical_classification biology Autoantibody Antibodies Monoclonal Galactose Rheumatoid Factor/ chemistry/genetics Cell Biology Hematology Oligosaccharide Isotype Molecular biology Cold Temperature chemistry Immunoglobulin G biology.protein Mutagenesis Site-Directed lipids (amino acids peptides and proteins) Antibody Immunoglobulin Heavy Chains Dimerization |
| Zdroj: | Blood, Vol. 99, No 8 (2002) pp. 2922-2928 |
| ISSN: | 0006-4971 |
| Popis: | Autoantibodies of the cryoprecipitating IgG3 isotype have been shown to play a significant role in the development of murine lupus–like autoimmune syndrome. At present, the structural basis of IgG3 cryoprecipitation and its role in autoantibody pathogenicity remain to be defined. Using molecular variants of an IgG3 monoclonal rheumatoid factor, 6-19, derived from an autoimmune MRL-Faslpr mouse, we have investigated the implication of charged residues in the heavy-chain variable (VH) region, potential CH3-linked oligosaccharides, and galactosylation of CH2-linked oligosaccharides in its cryoglobulin activity. The cryoglobulin activity of the IgG3 6-19 mutant bearing more negatively charged residues at VH 6 and 23 was found to be reduced but still highly significant, whereas that of the mutant lacking a potential CH3 glycosylation site remained unchanged. In marked contrast, IgG3 6-19 variants obtained from 6-19 heavy-chain transgenic mice displayed barely detectable cryoglobulin activity associated with an increased level of galactosylation in the CH2 oligosaccharide side chains. Thus, our data strongly suggest that the cryoglobulin activity of IgG3 6-19 autoantibody is critically determined by levels of galactosylation in the CH2 oligosaccharide side chains, whereas VH residues play a secondary role in 6-19 IgG3 cryoglobulin activity. |
| Databáze: | OpenAIRE |
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