Brown B K, Song W
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Traffic. 2001 Jun;2(6):414-27. doi: 10.1034/j.1600-0854.2001.002006414.x.
The B cell antigen receptor (BCR) plays two central roles in B cell activation: to internalize antigens for processing and presentation, and to initiate signal transduction cascades that both promote B cells to enter the cell cycle and facilitate antigen processing by accelerating antigen transport. An early event in B cell activation is the association of BCR with the actin cytoskeleton, and an increase in cellular F-actin. Current evidence indicates that the organization of actin filaments changes in response to BCR-signaling, making actin filaments good candidates for regulation of BCR-antigen targeting. Here, we have analyzed the role of actin filaments in BCR-mediated antigen transport, using actin filament-disrupting reagents, cytochalasin D and latrunculin B, and an actin filament-stabilizing reagent, jasplakinolide. Perturbing actin filaments, either by disrupting or stabilizing them, blocked the movement of BCR from the plasma membrane to late endosomes/lysosomes. Cytochalasin D-treatment dramatically reduced the rate of internalization of BCR, and blocked the movement of the BCR from early endosomes to late endosomes/lysosomes, without affecting BCR-signaling. Thus, BCR-trafficking requires functional actin filaments for both internalization and movement to late endosomes/lysosomes, defining critical control points in BCR-antigen targeting.
B细胞抗原受体（BCR）在B细胞激活过程中发挥着两个核心作用：内化抗原以进行加工和呈递，以及启动信号转导级联反应，既促进B细胞进入细胞周期，又通过加速抗原运输来促进抗原加工。B细胞激活的早期事件是BCR与肌动蛋白细胞骨架的结合以及细胞内F-肌动蛋白的增加。目前的证据表明，肌动蛋白丝的组织会响应BCR信号而发生变化，这使得肌动蛋白丝成为调节BCR-抗原靶向的良好候选者。在这里，我们使用肌动蛋白丝破坏试剂细胞松弛素D和拉春库林B以及肌动蛋白丝稳定试剂茉莉酮酸甲酯，分析了肌动蛋白丝在BCR介导的抗原运输中的作用。通过破坏或稳定肌动蛋白丝来干扰肌动蛋白丝，会阻止BCR从质膜向晚期内体/溶酶体的移动。细胞松弛素D处理显著降低了BCR的内化速率，并阻止了BCR从早期内体向晚期内体/溶酶体的移动，而不影响BCR信号传导。因此，BCR运输需要功能性肌动蛋白丝来进行内化和向晚期内体/溶酶体的移动，这定义了BCR-抗原靶向中的关键控制点。
