IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates

IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates
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DOI:
10.1073/pnas.0601407103
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发表时间:
2006-07-11
影响因子:
11.1
通讯作者:
Flajnik, Martin
Flajnik, Martin
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ohta, Yuko;Flajnik, Martin

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IgD自40多年前被发现以来,一直是一个神秘的IG类,也是免疫学专业学生的祸根。它在哺乳动物和鸟类中的斑点出现以及在硬骨鱼中发现与IgD相似的同种型是令人困惑的。我们已经确定了IgD重(H)链(三角洲)从两栖动物热带爪蟾在检查IgH基因座。非洲爪蟾δ基因与哺乳动物中的IgM基因位于相同的位置,即3'端,并且仅在脾脏中以低水平表达,主要作为表面IgM(+)细胞的跨膜受体。我们的数据表明,青蛙IgD表达在成熟的B细胞,像在小鼠/人。出乎意料的是,非洲爪蟾IgD与IgW是直系同源的,IgW是一种仅在软骨鱼和肺鱼中发现的IG同种型,这表明IgD/W与IgM一样,存在于所有现存有颚脊椎动物的祖先中。与IgM形成鲜明对比的是,IgD/W在进化上是不稳定的,显示出许多结构域的重复/缺失,存在多种剪接形式,主要以分泌或跨膜形式存在,或以物种特异性方式丢失整个基因。我们的研究表明,IgD/W发挥了不同的作用,在不同的脊椎动物类群自适应性免疫系统的开始,它可能已被保存为一个灵活的轨迹在进化的时间,以补充坚定的IgM。
IgD has remained a mysterious Ig class and a bane to immunology students since its discovery > 40 years ago. Its spotty occurrence in mammals and birds and the discovery of an isotype with similarities to IgD in bony fish are perplexing. We have identified IgD heavy (H) chain (delta) from the amphibian Xenopus tropicalis during examination of the IgH locus. The Xenopus delta gene is in the same position, immediately 3' of the IgM gene, as in mammals, and it is expressed only in the spleen at low levels, primarily as a transmembrane receptor by surface IgM(+) cells. Our data suggest that frog IgD is expressed on mature B cells, like in mouse/human. Unexpectedly, Xenopus IgD is orthologous to IgW, an Ig isotype found only in cartilaginous fish and lungfish, demonstrating that IgD/W, like IgM, was present in the ancestor of all living jawed vertebrates. In striking contrast to IgM, IgD/W is evolutionarily labile, showing many duplications/deletions of domains, the presence of multiple splice forms, existence as predominantly a secretory or transmembrane form, or loss of the entire gene in a species-specific manner. Our study suggests that IgD/W has played varied roles in different vertebrate taxa since the inception of the adaptive immune system, and it may have been preserved as a flexible locus over evolutionary time to complement steadfast IgM.