HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta(2)-microglobulin (beta(2)m) double transgenic mice with disrupted mouse beta(2)m

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 beta(2)-microglobulin (beta(2)m) gene was replaced with transgenic human beta(2)m 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 beta(2)m 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' HCB in the disease process.