Induction of microthrombotic thrombocytopenia in normal mice by transferring a platelet-reactive, monoclonal anti-gp70 autoantibody established from MRL/lpr mice: an autoimmune model of thrombotic thrombocytopenic purpura

Clin Exp Immunol. 2000 Jan;119(1):47-56. doi: 10.1046/j.1365-2249.2000.01116.x.


MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop immune complex-mediated glomerulonephritis and thrombocytopenia. Although the presence of cross-reactive anti-phospholipid antibodies in sera of MRL/lpr mice has been demonstrated, possible relationships between detected autoantibodies and the development of thrombocytopenia have not been elucidated. Recent genetic analyses in a few different strains of lupus-prone mice have pointed out a close correlation between autoantibodies reactive with endogenous retroviral env gene product, gp70, and the development and severity of glomerulonephritis. In the process of establishing possibly nephritogenic anti-gp70 autoantibody-producing hybridoma cells from MRL/lpr mice, we identified an IgG2a-producing anti-gp70 hybridoma clone that induced microvascular intraluminal platelet aggregation, thrombocytopenia, and amenia upon transplantation into syngeneic non-autoimmune mice. This and two other anti-gp70 antibodies bound onto the surface of mouse platelets, and purified IgG2a of the anti-gp70 autoantibody induced glomerular lesions with characteristics of thrombotic thrombocytopenic purpura when injected into non-autoimmune mice. The pathogenic anti-gp70 autoantibody specifically precipitated a platelet protein with an approximate relative molecular mass of 40 000.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Autoantibodies / administration & dosage*
  • Blood Platelets / immunology*
  • Cell Line
  • Female
  • Friend murine leukemia virus / immunology
  • Glomerulonephritis / etiology
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Hybridomas / immunology
  • Immunization, Passive
  • Immunoglobulin G / administration & dosage
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Platelet Aggregation / immunology
  • Purpura, Thrombotic Thrombocytopenic / etiology*
  • Purpura, Thrombotic Thrombocytopenic / immunology
  • Purpura, Thrombotic Thrombocytopenic / pathology
  • Viral Envelope Proteins / immunology


  • Antibodies, Monoclonal
  • Autoantibodies
  • Immunoglobulin G
  • Viral Envelope Proteins