HLA - B 27 Heavy Chains Contribute to Spontaneous Inflammatory Disease in B 27 / human b 2 - Microglobulin ( b 2 m ) Double Transgenic Mice with Disrupted Mouse

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 b 2 -microglobulin ( b 2 m) gene was replaced with transgenic human b 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 b 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’ HCs in the disease process. ( J. Clin. Invest. 1996. 98:2746–2755.)