基于近距离标记的 MHC II 类和 CD37 是具有免疫功能的 B 细胞受体近端蛋白。

Q3 Medicine
Sean Hoeger, Lisa A. Drake, J. Drake
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引用次数: 0

摘要

BCR 可使 Ag 驱动的 B 细胞活化,随后进行 Ag 内吞、处理和呈递,以招募 T 细胞的帮助。BCR 信号传导和内吞的核心驱动因素是受体胞质尾部的基团(主要是 CD79)。不过,BCR 的功能也可由其他近端细胞元素(如 CD20 和膜脂质微域)调节。为了识别更多可调节 BCR 功能的蛋白质,我们使用了一种基于邻近性的生物素化技术,并搭配质谱法来识别小鼠 IgM BCR 的分子邻近物。这些相邻蛋白包括 MHC II 类分子、整合素、各种转运体和膜微域蛋白。II 类分子(其中一些是不变链相关的新生 II 类分子)是很容易检测到的 BCR 邻体。这一发现与有关 BCR-Ⅱ类在细胞内结合的报道一致。BCR 还与多种参与膜微域形成的蛋白质非常接近,包括 CD37、筏林和 Ig 超家族成员 8。已知 CD37 基因敲除小鼠的 T 细胞依赖性体液免疫缺陷表明 CD37 在 BCR 功能中的作用。与这一观点相一致的是,基于 CRISPR 技术敲除 B 细胞系中 CD37 的表达会增强 BCR 信号转导,减缓 BCR 的内吞,并抑制肽类 II 复合物的形成。这些结果表明,BCR分子邻近物会影响膜介导的BCR功能。总之,通过基于邻近性的标记技术,发现了多种以前未知的 BCR 分子邻近物,包括能调节 BCR 功能的四泛蛋白蛋白 CD37。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proximity-Based Labeling Identifies MHC Class II and CD37 as B Cell Receptor-Proximal Proteins with Immunological Functions.
The BCR allows for Ag-driven B cell activation and subsequent Ag endocytosis, processing, and presentation to recruit T cell help. Core drivers of BCR signaling and endocytosis are motifs within the receptor's cytoplasmic tail (primarily CD79). However, BCR function can be tuned by other proximal cellular elements, such as CD20 and membrane lipid microdomains. To identify additional proteins that could modulate BCR function, we used a proximity-based biotinylation technique paired with mass spectrometry to identify molecular neighbors of the murine IgM BCR. Those neighbors include MHC class II molecules, integrins, various transporters, and membrane microdomain proteins. Class II molecules, some of which are invariant chain-associated nascent class II, are a readily detected BCR neighbor. This finding is consistent with reports of BCR-class II association within intracellular compartments. The BCR is also in close proximity to multiple proteins involved in the formation of membrane microdomains, including CD37, raftlin, and Ig superfamily member 8. Known defects in T cell-dependent humoral immunity in CD37 knockout mice suggest a role for CD37 in BCR function. In line with this notion, CRISPR-based knockout of CD37 expression in a B cell line heightens BCR signaling, slows BCR endocytosis, and tempers formation of peptide-class II complexes. These results indicate that BCR molecular neighbors can impact membrane-mediated BCR functions. Overall, a proximity-based labeling technique allowed for identification of multiple previously unknown BCR molecular neighbors, including the tetraspanin protein CD37, which can modulate BCR function.
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来源期刊
CiteScore
3.70
自引率
0.00%
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0
审稿时长
4 weeks
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