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 hu man 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 wher e endogenous beta(2)-microglobulin (beta(2)m) gene was replaced with t ransgenic human beta(2)m gene. These mice showed cell surface expressi on of HLA-B27 similar to that of human peripheral blood mononuclear ce lls, In addition, free heavy chains (HCs) of HLA-B27 were also express ed on thymic epithelium and on a subpopulation of B27-expressing PBLs, These mice developed spontaneous arthritis and nail changes in the re ar paws, Arthritis occurred primarily in male animals and only when mi ce were transferred from the pathogen-free barrier facility to the con ventional area, Transgenic mice expressing HLA-B27 with mouse beta(2)m have undetectable levels of free HCs on the cell surface and do not d evelop arthritis. In vivo treatment with anti-HC-specific antibody del ayed the onset of disease, Our data demonstrate specific involvement o f HLA-B27 'free' HCB in the disease process.