The role of FcgammaR signaling in the K/B x N serum transfer model of arthritis.
Spontaneous arthritis in the KRN transgenic mouse (K/BxN) model is due to the autoreactivity of the transgenic TCR and subsequent induction of autoantibodies directed against glucose-6-phosphate isomerase. These autoantibodies transfer clinically apparent arthritis into most recipient mouse strains and systemic catabolism of the transferred Abs attenuates paw swelling. Although mice deficient in the common gamma-chain of the FcgammaR did not show clinical synovitis after receiving K/BxN sera, erosive lesions in the bone still developed. Further analysis demonstrated that FcgammaRII(-/-) mice manifested accelerated arthritis whereas the FcgammaRIII(-/-) mice had a more slowly progressing arthritis. Paw swelling required FcgammaR expression by bone marrow-derived cells and mast cells substantially contributed to the acute phase of paw swelling. In the K/BxN serum transfer model of arthritis, there is a clinically apparent acute phase, which is modulated by FcgammaRII and FcgammaRIII, and a subacute component, which results in bone erosion, even in the absence of FcgammaR signaling.
Corr
Maripat
M
Division of Rheumatology, Allergy, and Immunology and Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093, USA. mcorr@ucsd.edu
Crain
Brian
B
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000008:administration & dosage / Q000378:metabolism; D001842:Bone and Bones / Q000473:pathology; D019672:Genes, T-Cell Receptor; D007116:Immunization, Passive; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011828:Radiation Chimera; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000473:pathology
D001323:Autoantibodies; D017452:Receptors, IgG