The role of Ig-α/β in B cell antigen receptor internalization
The role of Ig-α/β in B cell antigen receptor internalization
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DOI：
10.1016/j.imlet.2010.09.001
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发表时间：
2010-11-30
影响因子：
4.4
通讯作者：
Matsuuchi, Linda
中科院分区：
文献类型：
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作者：
Jang, Caren;Machtaler, Steven;Matsuuchi, Linda
B细胞受体在B淋巴细胞表面表达，在那里它可以结合抗原，然后传递调节活化、生长和分化的信号。这些信号可以诱导许多细胞骨架重排，导致动态细胞过程，包括结合抗原的内化，然后被加工并呈递给MHC H上的T细胞。胞质结构域在信号传导方面已被充分研究，但它们在BCR内化和运输中的作用尚不清楚。我们假设IG α和IG β胞质结构域对于4链BCR的正常内化和运输是重要的。使用IG α和IG β缺陷的鼠淋巴细胞系与一组IG α和IG β突变体沿着表达mIgM，以比较它们的突变体。内化和亚细胞定位在这里，我们表明，IG α和IG β胞质结构域都足以内化，尽管在这一过程中，伊加是占主导地位的。我们还表明，内化信号包含在IG α和IG β的第一个胞质酪氨酸残基之后的区域，分别为Y176和Y195。我们还表明，通常包含在IG α中的4个氨基酸基序ITAM足以挽救异常内化在受体运输方面，每个胞质结构域足以运输到溶酶体区室，但正常的运输速率可能需要IG α和IG β的串联效应（C）2010 Elsevier B V保留所有权利
The B cell antigen receptor (BCR) is expressed on the surface of B lymphocytes where it can bind antigen then transmit signals which regulate activation growth and differentiation These signals can induce a number of cytoskeletal rearrangements leading to dynamic cellular processes including internalization of the bound antigen which is then processed and presented to T cells on MHC H The relative importance of regions within the Ig alpha and Ig beta cytoplasmic domains has been well studied in terms of signaling but their roles in BCR internalization and trafficking are less clear We hypothesize that the Ig alpha and Ig beta cytoplasmic domains is important for normal internalization and trafficking of the 4 chain BCR An Ig alpha and Ig beta deficient murine lymphoid cell line was used to express mIgM along with a panel of Ig alpha and Ig beta mutants in order to compare their internalization and subcellular localization Here we show that the Ig alpha and Ig beta cytoplasmic domains are each sufficient for internalization though Iga is dominant in this process We also show that the internalization signal is contained in a region past the first cytoplasmic tyrosine residue of Ig alpha and Ig beta Y176 and Y195 respectively We also show that a 4 amino acid motif normally contained within the Ig alpha ITAM is sufficient to rescue aberrant internalization In terms of receptor trafficking each cytoplasmic domain is sufficient for trafficking to lysosomal compartments but that a normal rate of trafficking likely requires the tandem effects of both Ig alpha and Ig beta (C) 2010 Elsevier B V All rights reserved