Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum.
Defective Fc gamma RII gene expression in macrophages of NOD mice: genetic linkage with up-regulation of IgG1 and IgG2b in serum.
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NOD 小鼠巨噬细胞中 Fc gamma RII 基因表达缺陷：与血清中 IgG1 和 IgG2b 上调的遗传联系。
DOI：
10.4049/jimmunol.157.10.4707
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发表时间：
1996
影响因子：
4.4
通讯作者：
H. Garchon
中科院分区：
文献类型：
--
作者：
J. Luan;R. Monteiro;C. Sautés;G. Fluteau;L. Eloy;W. Fridman;J. Bach;H. Garchon
NOD 小鼠品系中 IgG 血清水平增加的数量性状基因座被映射到远端染色体 1，靠近编码 IgG Fc 部分（Fc gamma RII）的低亲和力 II 型受体的 fcgr2 基因座。与 C57BL/6 (B6) 小鼠相比，NOD 巨噬细胞中 Fc gamma RII 的膜插入 (b2) 和可溶性 (b3) 亚型的表达显着降低。相比之下，B 细胞特异性 (Fc gamma RIIb1) 同种型仅略有减少，而 Fc gamma RIII 没有改变。这种 Fc gamma RII 调节缺陷由 fcgr2 或紧密相连的基因座顺式编码，发生在 mRNA 水平，并与 fcgr2 基因启动子中的多个突变相关。与此缺陷相关，NOD 和同源 B6.NOD-fcgr2 小鼠的巨噬细胞与 IgG1 和 IgG2b 而非 IgG2a 调理红细胞的结合严重受损，但在 NOD.B6-fcgr2 同源小鼠的巨噬细胞中正常，表明 Fc gamma RII 在 IgG1 和 IgG2b 同种型的结合中发挥着不可或缺的作用。同样，与 NOD.B6-fcgr2 同源小鼠相比，NOD 中 IgG1 和 IgG2b 而非 IgG2a 的血清水平上调。这些发现表明巨噬细胞 Fc gamma RII 可能通过分解代谢调节血清 IgG1 和 IgG2b，并验证了 NOD 菌株作为研究 Fc gamma RII 亚型功能的模型。
A quantitative trait locus for increased IgG serum levels in the NOD mouse strain was mapped to distal chromosome 1, close to the fcgr2 locus encoding the low-affinity type II receptor for the Fc portion of IgG (Fc gamma RII). Expression of membrane-inserted (b2) and soluble (b3) isoforms of Fc gamma RII was strongly decreased in macrophages of NOD compared with C57BL/6 (B6) mice. In contrast, B cell-specific (Fc gamma RIIb1) isoform was only slightly decreased and Fc gamma RIII was not altered. This Fc gamma RII regulatory defect was cis-encoded by fcgr2 or by a closely linked locus, occurred at the mRNA level, and was associated with multiple mutations in the fcgr2 gene promoter. In relation with this defect, binding of IgG1- and IgG2b- but not IgG2a-opsonized RBC by macrophages of NOD and congenic B6.NOD-fcgr2 mice was severely impaired, but was normal in macrophages of NOD.B6-fcgr2 congenic mice, indicating that Fc gamma RII plays a nondispensable role in binding of IgG1 and IgG2b isotypes. Likewise, serum levels of IgG1 and IgG2b but not IgG2a were up-regulated in NOD compared with NOD.B6-fcgr2 congenic mice. These findings indicate that macrophage Fc gamma RII may regulate serum IgG1 and IgG2b through their catabolism, and validate the NOD strain as a model to investigate the functions of Fc gamma RII isoforms.