Influence of the isotype of the light chain on the properties of IgG
Influence of the isotype of the light chain on the properties of IgG
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DOI：
10.4049/jimmunol.168.1.224
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发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Morrison, SL
中科院分区：
文献类型：
--
作者：
Montaño, RF;Morrison, SL
人们普遍认为，Ab分子的H链的同型会影响其功能性质。我们现在已经研究了L链的同型对Ab分子的结构和功能特性的贡献。在这些研究中，小鼠抗丹酚Ab的L链可变区与人kappa或lambda恒定区连接，并与四种人IgG同型的鼠-人嵌合H链表达。所得的抗体作为完全组装的分子分泌，尽管如先前观察到的那样，具有kappa或lambda L链的IgG4也以HL半分子的形式分泌。然而，L链的同型可以影响细胞内组装的动力学，IgG1 lambda、IgG2 lambda和IgG4 lambda的组装比它们的fc对应物慢。L链的同型也会影响链间二硫键对还原剂攻击的敏感性，这些还原剂的作用取决于H链的同型。对于IgG2，而不是IgG1， -3和-4，L链的同型影响小鼠的清除率，IgG2 lambda的体内半衰期比IgG2 kappa短。λ和kappa分子在与半抗原丹酚的结合和解离动力学上也只有微小的差异。这些研究表明，1。对可变区相同抗体的结构和功能性质影响不大。
It is widely appreciated that the isotype of the H chain of the Ab molecule influences its functional properties. We have now investigated the contribution of the isotype of the L chain to the structural and functional properties of the Ab molecule. In these studies, the L chain variable region of a murine anti-dansyl Ab was joined to either human kappa or lambda constant region domains and expressed with mouse-human chimeric H chains of the four human IgG isotypes. The resulting Abs were secreted as fully assembled molecules although, as has been previously observed, IgG4 with either kappa or lambda L chains was also secreted as HL half-molecules. However, the isotype of the L chain can influence the kinetics of intracellular assembly with IgG1 lambda, IgG2 lambda, and IgG4 lambda assembling more slowly than their fc counterparts. The isotype of the L chain also influenced the susceptibility of the interchain disulfide bonds to attack by reducing agents with variable effects, depending on the isotype of the H chains. For IgG2, but not for IgG1, -3, and -4, the isotype of the L chain influenced the rate of clearance in mice, with IgG2 lambda having a shorter in vivo half-life than IgG2 kappa. Only slight differences were also observed between lambda and kappa molecules in their kinetics of binding to and dissociation from the hapten dansyl. These studies demonstrate that the isotype of the 1. chain has only a slight impact on the structural and functional properties of variable region identical Abs.