IgD can largely substitute for loss of IgM function in B cells
IgD can largely substitute for loss of IgM function in B cells
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DOI：
10.1038/31716
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发表时间：
1998-06-25
期刊：
影响因子：
64.8
通讯作者：
Brombacher, F
中科院分区：
文献类型：
--
作者：
Lutz, C;Ledermann, B;Brombacher, F
在骨髓B细胞发育过程中表达的第一个抗体亚型--IgM和IGD的u重链和德尔塔重链由一个共同的转录单位编码。晚期前B细胞表面mU链的表达使其进一步发育为未成熟的B细胞。Delta链的共表达和未成熟B细胞向周围的迁移最终导致幼稚成熟的IgM/IGD双阳性细胞的发育。虽然IgM在推动B细胞发育方面很重要(1)，但IGD的作用尚不清楚。在这里，我们研究了IGD的功能。我们通过删除mU产生了IgM缺陷小鼠(IgM(-/-)小鼠)。胚胎干细胞中的区域。IGM-/-小鼠表现出正常的B细胞发育和成熟，IGD取代了膜结合型和分泌型IgM。此外，在免疫或感染期间发生了特异性B细胞反应和同种类型转换。与B细胞缺陷的小鼠相比，IgM(-/-)小鼠通过产生中和免疫球蛋白而在水泡性口炎病毒感染中存活下来，但它们比野生型对照组更容易产生延迟的特异性免疫球蛋白反应。这些数据使我们得出结论，IGD在很大程度上能够替代IgM功能。
The mu and delta heavy chains of IgM and IgD, the first antibody isotypes expressed during bone-marrow B-cell development, are encoded by a common transcription unit. Expression of the mu chain on the surface of late pre-B cells allows their further development to immature B cells. Coexpression of the delta chain and emigration of the immature B cells to the periphery eventually leads to the development of naive mature IgM/IgD double-positive cells. Although IgM is important in driving B-cell development(1), the contribution of IgD is not clear. Here we investigate the function of IgD. We generated mice deficient in IgM (IgM(-/-) mice) by deleting the mu. region in embryonic stem cells. IgM-/- mice showed normal B-cell development and maturation, with IgD replacing membrane-bound and secretory IgM. Moreover, specific B-cell responses and isotype class switches occurred during immunization or infection. In contrast to mice deficient in B cells, IgM(-/-) mice survived infection with vesicular stomatitis virus by developing neutralizing immunoglobulins, but they were more susceptible than wild-type controls with delayed specific immunoglobulin responses. These data lead us to conclude that IgD is largely able to substitute for IgM functions.