HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.
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.
Khare
S D
SD
Department of Immunology, Mayo Clinic and Medical School, Rochester, Minnesota 55905, USA.
Hansen
J
J
Luthra
H S
HS
David
C S
CS
D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D017931:DNA Primers; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006724:Hoof and Claw / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D015796:HLA-B27 Antigen; D001613:beta 2-Microglobulin