INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Service de Néphrologie, Paris, France.
INSERM U1149, Centre de Recherche sur l'Inflammation (CRI), DHU Fire, Paris, France ELR8252 CNRS, Paris, France Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Paris, France AP-HP, Hôpital Bichat, Départment d'Hémato-immunologie, UF Dysfonctionnements Immunitaires, Paris, France.
Nephrol Dial Transplant. 2016 Aug;31(8):1235-42. doi: 10.1093/ndt/gfv335. Epub 2015 Sep 26.
Strait et al. described a novel mouse model of cryoglobulinaemia by challenging mice deficient in the immunoglobulin (Ig)G1 subclass (γ1(-) mice) with goat anti-mouse IgD [5]. The phenotype of wild-type mice was not remarkable, whereas γ1(-) mice developed IgG3 anti-goat IgG cryoglobulins as well as severe and lethal glomerulonephritis. Renal phenotype could not be rescued in γ1(-) mice by the deletion of C3, fragment crystalline γ receptor (FcγR) or J chain. On the other hand, early injection of IgG1, IgG2a or IgG2b inhibited the pathogenic effects of IgG3 in an antigen-dependent manner even in the absence of the FcγRIIb, an anti-inflammatory receptor. The authors concluded that the pathogenic role of IgG3 and the protective characteristic of IgG1 in this model were not explained by their abilities to bind to FcRs or effector molecules but are rather due to structural discrepancies enhancing the precipitation properties/solubility of IgG3/IgG1-containing immune complexes. The present article aims to discuss the current knowledge on IgG biology and the properties of IgGs explaining their differential propensity to acquire cryoglobulin activity.
斯特雷特等人通过用山羊抗小鼠 IgD 对缺乏 IgG1 亚类（γ1(-) 小鼠）的小鼠进行挑战，描述了一种新型的冷球蛋白血症小鼠模型[5]。野生型小鼠的表型不明显，而 γ1(-) 小鼠则产生 IgG3 抗山羊 IgG 冷球蛋白血症以及严重和致命的肾小球肾炎。在 γ1(-) 小鼠中，通过缺失 C3、片段结晶 γ 受体（FcγR）或 J 链，无法挽救肾脏表型。另一方面，即使在缺乏抗炎受体 FcγRIIb 的情况下，早期注射 IgG1、IgG2a 或 IgG2b 也以抗原依赖性方式抑制 IgG3 的致病作用。作者得出结论，在该模型中 IgG3 的致病作用和 IgG1 的保护特征不是由其与 FcR 或效应分子结合的能力解释的，而是由于结构差异增强了含有 IgG3/IgG1 的免疫复合物的沉淀特性/溶解度。本文旨在讨论 IgG 生物学的现有知识以及解释其获得冷球蛋白活性的不同倾向的 IgGs 的特性。
