Abstract：
The B cell receptor (BCR) signals together with a multi-component co-receptor complex to initiate B cell activation in response to antigen binding. Here, we take advantage of peroxidase-catalyzed proximity labeling combined with quantitative mass spectrometry to track co-receptor signaling dynamics in Raji cells from 10 s to 2 h after BCR stimulation. This approach enables tracking of 2,814 proximity-labeled proteins and 1,394 phosphosites and provides an unbiased and quantitative molecular map of proteins recruited to the vicinity of CD19, the signaling subunit of the co-receptor complex. We detail the recruitment kinetics of signaling effectors to CD19 and identify previously uncharacterized mediators of B cell activation. We show that the glutamate transporter SLC1A1 is responsible for mediating rapid metabolic reprogramming and for maintaining redox homeostasis during B cell activation. This study provides a comprehensive map of BCR signaling and a rich resource for uncovering the complex signaling networks that regulate activation.
摘要：
B细胞受体(BCR)与多组分共受体复合物一起发信号以响应于抗原结合而启动B细胞活化。这里,我们利用过氧化物酶催化的邻近标记结合定量质谱来跟踪BCR刺激后10s至2hRaji细胞中的共受体信号传导动力学。这种方法能够跟踪2,814个邻近标记的蛋白质和1,394个磷酸位点，并提供了募集到CD19附近的蛋白质的无偏定量分子图谱，CD19是共受体复合物的信号亚基。我们详细介绍了CD19信号效应子的募集动力学，并鉴定了以前未表征的B细胞激活介质。我们表明，谷氨酸转运体SLC1A1负责介导快速代谢重编程，并在B细胞活化过程中维持氧化还原稳态。这项研究提供了BCR信号的全面图谱和丰富的资源，用于揭示调节激活的复杂信号网络。
