Díaz de Ståhl Teresita, Andrén Maria, Martinsson Pernilla, Verbeek J Sjef, Kleinau Sandra
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Eur J Immunol. 2002 Oct;32(10):2915-22. doi: 10.1002/1521-4141(2002010)32:10<2915::AID-IMMU2915>3.0.CO;2-4.
Circulating immune complexes are implicated in the pathogenesis of rheumatic immune disorders and the interaction of these immune complexes with IgG Fc receptors (FcgammaR) seems to be a determining step in the initiation of the inflammatory process. Mice deficient in the FcRgamma-chain, and thus lacking multiple FcR, have previously been shown to be protected from collagen-induced arthritis (CIA). However, the relative contribution of the different FcgammaR has not been identified. In this study, we investigated the expression and contribution of FcgammaRIII, the activating low-affinity FcgammaR in the development of CIA. Wild-type and FcgammaRIII-deficient DBA/1 (FcgammaRIII(-/-)) mice were immunized with bovine collagen type II (BCII) in Freund's complete adjuvant and arthritis development was evaluated by clinical and histological examinations. We found that FcgammaRIII(-/-) mice developed virtually no arthritis in contrast to wild-type mice, the majority of which developed severe CIA. Although resistant to CIA, the humoral and cellular responses to BCII in FcgammaRIII(-/-) mice were similar to that seen in wild-type controls. FcgammaRIII expression was studied on sections from normal joints of FcgammaRII-deficient DBA/1 mice stained with the mAb 2.4G2, specific for FcgammaRII and FcgammaRIII. FcgammaRIII was demonstrated in cells of the lining and sublining layer of the synovial membrane. We conclude that development of CIA requires FcgammaRIII and that expression of FcgammaRIII on synovial cells may contribute to the antibody-triggered inflammation in joints.
循环免疫复合物与风湿性免疫疾病的发病机制有关，这些免疫复合物与IgG Fc受体（FcγR）的相互作用似乎是炎症过程启动的决定性步骤。先前已证明，缺乏FcRγ链因而缺乏多种FcR的小鼠对胶原诱导的关节炎（CIA）具有抵抗力。然而，不同FcγR的相对作用尚未明确。在本研究中，我们调查了活化性低亲和力FcγR FcγRIII在CIA发病过程中的表达及作用。用弗氏完全佐剂中的牛II型胶原（BCII）免疫野生型和FcγRIII缺陷型DBA/1（FcγRIII(-/-)）小鼠，并通过临床和组织学检查评估关节炎的发展。我们发现，与大多数发生严重CIA的野生型小鼠相比，FcγRIII(-/-)小鼠几乎不发生关节炎。尽管对CIA有抵抗力，但FcγRIII(-/-)小鼠对BCII的体液和细胞反应与野生型对照相似。用对FcγRII和FcγRIII特异的单克隆抗体2.4G2对FcγRII缺陷型DBA/1小鼠的正常关节切片进行染色，研究FcγRIII的表达。在滑膜衬里层和衬里下层的细胞中证实有FcγRIII。我们得出结论，CIA的发生需要FcγRIII，滑膜细胞上FcγRIII的表达可能导致关节中抗体引发的炎症。
