Scientific article

A transgenic mouse model of autoimmune glomerulonephritis and necrotizing arteritis associated with cryoglobulinemia

Published inThe Journal of immunology, vol. 169, no. 8, p. 4644-4650
Publication date2002

Mice implanted with hybridoma secreting 6-19 IgG3 anti-IgG2a rheumatoid factor (RF) with cryoglobulin activity develop acute glomerulonephritis and cutaneous leukocytoclastic vasculitis. As the RF activity is implicated in the skin, but not glomerular lesions, it is still unclear whether the renal pathogenicity is determined by 6-19 H chains alone or their combination with L chains. To address this question, we have generated transgenic mice expressing only the H chain gene or both H and L chain genes of the 6-19 IgG3 anti-IgG2a RF and determined the development of glomerular and vascular lesions. H-single and H/L-double transgenic mice displayed comparable high amounts of IgG3 cryoglobulins, but only H/L-double transgenic mice having 10-fold higher levels of IgG3 anti-IgG2a RF progressively developed chronic, lethal glomerulonephritis. The severe glomerular lesions observed at 8-10 mo of age were very heterogeneous (membranoproliferative changes, crescents, and sclerosis); in addition, one-third of them had necrotizing arteritis in the kidneys and skeletal muscles. These renal and vascular changes were very different from those observed in the acute cryoglobulinemia, characterized by mainly "wire-loop" glomerular lesions and a cutaneous leukocytoclastic form of vasculitis. Thus, our data demonstrate the importance of a unique combination of the H and L chains for the expression of the pathogenic activity of IgG3 cryoglobulins and that a single autoantibody is able to induce different types of glomerular and vascular complications, depending on its production levels and kinetics.

  • Animals
  • Antibodies, Anti-Idiotypic/biosynthesis
  • Arteritis/genetics/ immunology/pathology
  • Autoantibodies/biosynthesis
  • Autoimmune Diseases/genetics/ immunology/pathology
  • Cryoglobulinemia/genetics/ immunology/pathology
  • Disease Models, Animal
  • Glomerulonephritis/genetics/ immunology/pathology
  • Hybridomas/immunology/secretion/transplantation
  • Immunoglobulin G/biosynthesis/genetics/immunology
  • Immunoglobulin Heavy Chains/genetics
  • Immunoglobulin Light Chains/genetics
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred MRL lpr
  • Mice, Transgenic
  • Necrosis
  • Rheumatoid Factor/genetics/immunology
  • Vasculitis, Leukocytoclastic, Cutaneous/genetics/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
KIKUCHI, Shuichi et al. A transgenic mouse model of autoimmune glomerulonephritis and necrotizing arteritis associated with cryoglobulinemia. In: The Journal of immunology, 2002, vol. 169, n° 8, p. 4644–4650. doi: 10.4049/jimmunol.169.8.4644
Updates (1)
ISSN of the journal0022-1767

Technical informations

Creation08/27/2010 1:35:07 PM
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Update time03/14/2023 4:03:58 PM
Status update03/14/2023 4:03:58 PM
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