HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m

J Clin Invest. 1996 Dec 15;98(12):2746-55. doi: 10.1172/JCI119100.


MHC class I allele, HLA-B27, is strongly associated with a group of human diseases called spondyloarthropathies. Some of these diseases have an onset after an enteric or genitourinary infection. In the present study, we describe spontaneous disease in HLA-B27 transgenic mice where endogenous beta2-microglobulin (beta2m) gene was replaced with transgenic human beta2m gene. These mice showed cell surface expression of HLA-B27 similar to that of human peripheral blood mononuclear cells. In addition, free heavy chains (HCs) of HLA-B27 were also expressed on thymic epithelium and on a subpopulation of B27-expressing PBLs. These mice developed spontaneous arthritis and nail changes in the rear paws. Arthritis occurred primarily in male animals and only when mice were transferred from the pathogen-free barrier facility to the conventional area. Transgenic mice expressing HLA-B27 with mouse beta2m have undetectable levels of free HCs on the cell surface and do not develop arthritis. In vivo treatment with anti-HC-specific antibody delayed the onset of disease. Our data demonstrate specific involvement of HLA-B27 'free' HCs in the disease process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis / genetics
  • Arthritis / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • DNA Primers
  • Disease Models, Animal
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Gene Expression Regulation / genetics
  • HLA-B27 Antigen / metabolism*
  • Hoof and Claw / metabolism
  • Humans
  • Inflammation / metabolism*
  • Leukocytes / metabolism
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Polymerase Chain Reaction
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / metabolism*


  • DNA Primers
  • HLA-B27 Antigen
  • beta 2-Microglobulin