Role of galactosylation in the renal pathogenicity of murine immunoglobulin G3 monoclonal cryoglobulins.

Cryoglobulin activity associated with murine immunoglobulin G3 (IgG3) has been shown to play a significant role in the development of murine lupuslike glomerulonephritis. A fraction, but not all, IgG3 monoclonal antibodies are capable of inducing a severe acute lupuslike glomerulonephritis as a result of direct localization of IgG3 cryoglobulins, suggesting the importance of qualitative features of cryoglobulins in their nephritogenic activities. Here a remarkable difference is shown in the renal pathogenicity of 2 murine IgG3 monoclonal cryoglobulins, identical in the amino acid sequences of their heavy and light chains but different in galactosylation patterns of oligosaccharide side chains because of their synthesis in different myeloma cells. The antibody lacking the capacity to induce severe glomerulonephritis displayed an increased proportion of galactosylated heavy chains. Changes in conformation, as revealed by gel filtration analysis, reduced cryoglobulin activity, and accelerated clearance could account for the lack of the renal pathogenicity of the more galactosylated variant. This observation provides a direct demonstration for the role of IgG galactosylation in the pathogenic potential of cryoglobulins. (Blood. 2001;97:3537-3543)

[1]  M. Cogné,et al.  Heavy and light chain primary structures control IgG3 nephritogenicity in an experimental model for cryocrystalglobulinemia. , 2000, Blood.

[2]  S. Izui,et al.  Role of neutrophils in murine cryoglobulinemia , 1998, Inflammation Research.

[3]  D. Panka.  Glycosylation is influential in murine IgG3 self-association. , 1997, Molecular immunology.

[4]  D. Isenberg,et al.  Agalactosyl IgG and β‐1,4‐galactosyltransferase gene expression in rheumatoid arthritis patients and in the arthritis‐prone MRL lpr/lpr mouse , 1996, Immunology.

[5]  S. Izui,et al.  Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. , 1996, The Journal of clinical investigation.

[6]  T. Berney,et al.  Polymorphonuclear leukocytes play a key role in the generation of "wire-loop" lesions induced by a murine IgG3 rheumatoid factor. , 1996, Kidney international.

[7]  T. Fujita,et al.  A Novel Human Serum Lectin with Collagen- and Fibrinogen-like Domains That Functions as an Opsonin (*) , 1996, The Journal of Biological Chemistry.

[8]  A. Sappino,et al.  Induction of plasminogen activator inhibitor type 1 in murine lupus-like glomerulonephritis. , 1995, Kidney international.

[9]  R. Dwek,et al.  Glycobiology: 'the function of sugar in the IgG molecule'. , 1995, Journal of anatomy.

[10]  R. Dwek,et al.  Glycosylation changes of IgG associated with rheumatooid arthritis can activate complement via the mannose-binding protein , 1995, Nature Medicine.

[11]  D. Salant,et al.  The effect of VH residues 6 and 23 on IgG3 cryoprecipitation and glomerular deposition , 1995, European journal of immunology.

[12]  S L Morrison,et al.  Effect of altered CH2-associated carbohydrate structure on the functional properties and in vivo fate of chimeric mouse-human immunoglobulin G1 , 1994, The Journal of experimental medicine.

[13]  R. Dwek,et al.  Agalactosyl glycoforms of IgG autoantibodies are pathogenic. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  T. Berney,et al.  Glomerulopathy induced by IgG3 anti-trinitrophenyl monoclonal cryoglobulins derived from non-autoimmune mice. , 1994, Kidney international.

[15]  J. Axford,et al.  Differential B lymphocyte galactosyltransferase activity in the MRL mouse model of rheumatoid arthritis. , 1994, Autoimmunity.

[16]  M. Ono,et al.  Induction of different types of glomerulonephritis by monoclonal antibodies derived from an MRL/lpr lupus mouse. , 1993, The American journal of pathology.

[17]  M. Nose,et al.  An MRL/MpJ-lpr/lpr substrain with a limited expansion of lpr double-negative T cells and a reduced autoimmune syndrome. , 1993, International immunology.

[18]  S. Izui,et al.  Immunoglobulin heavy chain constant region determines the pathogenicity and the antigen-binding activity of rheumatoid factor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Takahashi Satoru,et al.  Cloning and cDNA sequence analysis of nephritogenic monoclonal antibodies derived from an MRL/lpr lupus mouse , 1993 .

[20]  T. Mizuochi.  Microscale sequencing of N-linked oligosaccharides of glycoproteins using hydrazinolysis, Bio-Gel P-4, and sequential exoglycosidase digestion. , 1993, Methods in molecular biology.

[21]  S. Takahashi,et al.  Cloning and cDNA sequence analysis of nephritogenic monoclonal antibodies derived from an MRL/lpr lupus mouse. , 1993, Molecular immunology.

[22]  T. Fujita,et al.  Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease , 1992, The Journal of experimental medicine.

[23]  Wayne A. Hendrickson,et al.  Structure of a C-type mannose-binding protein complexed with an oligosaccharide , 1992, Nature.

[24]  K. Titani,et al.  Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. , 1992, The Journal of biological chemistry.

[25]  T. Berney,et al.  Induction of "wire-loop" lesions by murine monoclonal IgG3 cryoglobulins. , 1992, Kidney international.

[26]  T. Berney,et al.  Selective pathogenicity of murine rheumatoid factors of the cryoprecipitable IgG3 subclass. , 1992, International immunology.

[27]  S. Takahashi,et al.  IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis. , 1991, Journal of immunology.

[28]  Klaus Rajewsky,et al.  A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene , 1991, Nature.

[29]  F. Spertini,et al.  Cryoglobulinemia induced by a murine IgG3 rheumatoid factor: skin vasculitis and glomerulonephritis arise from distinct pathogenic mechanisms. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[30]  A. Cooke,et al.  Glycosylation of IgG, immune complexes and IgG subclasses in the MRL‐lpr/lpr mouse model of rheumatoid arthritis , 1990, European journal of immunology.

[31]  K. Titani,et al.  Structural changes in the oligosaccharide chains of IgG in autoimmune MRL/Mp-lpr/lpr mice. , 1990, Journal of immunology.

[32]  A. Kobata,et al.  Kinetic study of a galactosyltransferase in the B cells of patients with rheumatoid arthritis. , 1990, International immunology.

[33]  F. Spertini,et al.  Prevention of murine cryoglobulinemia and associated pathology by monoclonal anti-idiotypic antibody. , 1989, Journal of immunology.

[34]  P. Lachmann,et al.  A library of oligosaccharide probes (neoglycolipids) from N-glycosylated proteins reveals that conglutinin binds to certain complex-type as well as high mannose-type oligosaccharide chains. , 1989, The Journal of biological chemistry.

[35]  F. Spertini,et al.  IgG3 is the major source of cryoglobulins in mice. , 1989, Journal of immunology.

[36]  J. Rothbard,et al.  T-cell reactivity in myasthenia gravis. , 1989, Journal of autoimmunity.

[37]  G. Winter,et al.  Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Dwek,et al.  A comparative analysis of disease-associated changes in the galactosylation of serum IgG. , 1989, Journal of autoimmunity.

[39]  F. Spertini,et al.  Inhibition of cryoprecipitation of murine IgG3 anti‐dinitrophenyl (DNP) monoclonal antibodies by anionic DNP‐amino acid conjugates , 1989, European journal of immunology.

[40]  J. Axford,et al.  REDUCED B-CELL GALACTOSYLTRANSFERASE ACTIVITY IN RHEUMATOID ARTHRITIS , 1987, The Lancet.

[41]  F. Spertini,et al.  Cryoglobulinemia induced by monoclonal immunoglobulin G rheumatoid factors derived from autoimmune MRL/MpJ-lpr/lpr mice. , 1987, Journal of immunology.

[42]  R. Dwek,et al.  Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG , 1985, Nature.

[43]  F. Blattner,et al.  Structural analysis of the murine IgG3 constant region gene. , 1984, The EMBO journal.

[44]  M. Pierres,et al.  Rat monoclonal antibodies to mouse IgG1, IgG2a, IgG2b, and IgG3 subclasses, and kappa chain isotypic determinants. , 1984, Hybridoma.

[45]  H. Wigzell,et al.  Biological significance of carbohydrate chains on monoclonal antibodies. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Neuberger.  Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells. , 1983, The EMBO journal.

[47]  S. Morrison,et al.  Immunoglobulin gene expression in transformed lymphoid cells. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[48]  A. Shimizu,et al.  Structural and numerical variations of the carbohydrate moiety of immunoglobulin G. , 1982, Journal of immunology.

[49]  D. Baltimore,et al.  Somatic variants of murine immunoglobulin λ light chains , 1982, Nature.

[50]  K. Rajewsky,et al.  Analysis of the repertoire of anti‐(4‐hydroxy‐3‐nitro‐phenyl)acetyl (NP) antibodies in C 57 BL/6 mice by cell fusion. II. Characterization of idiotopes by monoclonal anti‐idiotope antibodies , 1979, European journal of immunology.

[51]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[52]  J. Clauvel,et al.  Biologic and clinical significance of cryoglobulins. A report of 86 cases. , 1974, The American journal of medicine.

[53]  M. Weigert,et al.  Mouse lambda-chain sequences. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[54]  H. Grey,et al.  A NEW MOUSE IMMUNOGLOBULIN: IGG3 , 1971, Journal of Experimental Medicine.