Syk-dependent actin dynamics regulate endocytic trafficking and processing of antigens internalized through the B-cell receptor
Syk-dependent actin dynamics regulate endocytic trafficking and processing of antigens internalized through the B-cell receptor
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DOI：
10.1091/mbc.e06-12-1114
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发表时间：
2007-09-01
影响因子：
3.3
通讯作者：
Lennon-Dumenil, Ana-Maria
中科院分区：
文献类型：
--
作者：
Le Roux, Delphine;Lankar, Danielle;Lennon-Dumenil, Ana-Maria
抗原与B细胞受体（BCR）的结合诱导最终导致B淋巴细胞活化的多个信号级联。此外，BCR调节允许抗原到达专门用于抗原加工的内吞区室的关键运输事件，即，其富含主要组织相容性因子II类（MHC II）和辅助分子如H2-DM。在这里，我们分析了酪氨酸激酶Syk在抗原加工和呈递中的作用，该激酶在BCR接合后被激活。我们发现，在缺乏Syk活性的细胞中，含有MHC II和H2-DM的隔间与运输BCR摄取抗原的囊泡的会聚受损。这种内吞运输的缺陷损害了Syk缺陷细胞从BCR内化抗原形成MHC II-肽复合物的能力。改变的内吞运输与Syk缺陷细胞响应BCR接合而正确重组其肌动蛋白细胞骨架的失败有关。我们建议，通过调节肌动蛋白动力学诱导BCR刺激后，Syk调节定位和运输的囊泡进行抗原加工和呈递所需的分子。
Antigen binding to the B-cell receptor (BCR) induces multiple signaling cascades that ultimately lead to B lymphocyte activation. In addition, the BCR regulates the key trafficking events that allow the antigen to reach endocytic compartments devoted to antigen processing, i.e., that are enriched for major histocompatibility factor class II (MHC II) and accessory molecules such as H2-DM. Here, we analyze the role in antigen processing and presentation of the tyrosine kinase Syk, which is activated upon BCR engagement. We show that convergence of MHC II- and H2-DM-containing compartments with the vesicles that transport BCR-uptaken antigens is impaired in cells lacking Syk activity. This defect in endocytic trafficking compromises the ability of Syk-deficient cells to form MHC II-peptide complexes from BCR-internalized antigens. Altered endocytic trafficking is associated to a failure of Syk-deficient cells to properly reorganize their actin cytoskeleton in response to BCR engagement. We propose that, by modulating the actin dynamics induced upon BCR stimulation, Syk regulates the positioning and transport of the vesicles that carry the molecules required for antigen processing and presentation.