FcγRIV:: A novel FcR with distinct IgG subclass specificity
FcγRIV:: A novel FcR with distinct IgG subclass specificity
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DOI：
10.1016/j.immuni.2005.05.010
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发表时间：
2005-07-01
期刊：
影响因子：
32.4
通讯作者：
Ravetch, JV
中科院分区：
文献类型：
--
作者：
Nimmerjahn, F;Bruhns, P;Ravetch, JV
小鼠IgG亚类显示出体内活性的层次结构，其中IgG 2a和IgG 2b显示出最大的保护性和致病性。这些增强的活性部分是由于其结合新型的7链依赖性活化IgG Fc受体Fc γ RIV的能力。Fc γ RIV定位于Fc γ RII和Fc γ RIII之间的75 kb基因组区间;其表达仅限于髓系细胞，并以中等亲和力与IgG 2a和IgG 2b结合。未观察到与IgG 1或IgG 3的结合。阻断Fc γ RIV与致病性抗血小板抗体的结合足以保护小鼠免于抗体诱导的血小板减少症。因此，Fe γ R系统已经进化出不同的激活受体，对IgG亚类表现出选择性，其中IgG 1抗体仅依赖于Fe γ RIII，而IgG 2a和IgG 2b表现出优先依赖于Fe γ RIV激活。IgG亚类对Fc γ R的这些不同的结合亲和力解释了它们在体内的不同保护和致病活性。
Mouse IgG subclasses display a hierarchy of in vivo activities, with IgG2a and IgG2b showing the greatest protective and pathogenic properties. These enhanced activities result, in part, from their ability to bind to a novel, 7 chain-dependent, activating IgG Fc receptor, Fc gamma RIV. Fc gamma RIV maps in the 75 kb genomic interval between Fc gamma RII and Fc gamma RIII; its expression is restricted to myeloid lineage cells, and it binds to IgG2a and IgG2b with intermediate affinity. No binding to IgG1 or IgG3 was observed. Blocking Fc gamma RIV binding to pathogenic anti-platelet antibodies is sufficient to protect mice from antibody-induced thrombocytopenia. Thus, the Fc gamma R system has evolved distinct activation receptors displaying selectivity for IgG subclasses, with IgG1 antibodies exclusively dependent on Fc gamma RIII, whereas IgG2a and IgG2b show preferential dependence on Fc gamma RIV activation. These distinct binding affinities for the IgG subclasses to Fc gamma Rs account for their differential protective and pathogenic activities in vivo.