Intracellular Trafficking Of The B cell Antigen Receptor

B细胞抗原受体（BCR）在B细胞活化中起双重作用。第一种是启动信号级联，导致与B细胞激活相关的多种基因的转录。然而，仅通过BCR的信号传导不足以完全激活B细胞，为此B细胞需要抗原特异性辅助T细胞的功能。B细胞和T细胞的相互作用是通过T细胞抗原受体（TCR）在B细胞表面结合抗原肽- mhc II类复合物介导的。B细胞表达的MHC肽复合物由新合成的MHC II类分子和来源于BCR结合抗原的肽组装在细胞内的隔室中。我们之前的研究表明，BCR将抗原转运到细胞内腔室，在那里抗原被降解，肽类复合物被组装。BCR的信号传导和抗原转运功能是相互依赖的，因为BCR信号传导对于抗原正确和快速靶向II类含室是必要的。事实上，对于信号缺陷的BCR，抗原要么不被处理，要么抗原递送率显著降低。反过来，BCR的内化可能通过从细胞表面去除活化受体在调节信号传导中发挥重要作用。我们最近的研究表明，BCR的信号和抗原靶向功能可能是通过BCR与富含胆固醇的膜微结构域（称为脂筏）的关联来协调的。我们发现静息细胞中的BCR被排除在浓缩src家族激酶Lyn的筏中，这是信号启动所必需的。抗原结合后，BCR转运到筏中，与Lyn结合并启动信号传导。随后，BCR被内化并运输到II类肽装载室。我们了解到，受体的内化在B细胞发育过程中受到B细胞辅助受体的控制，这些受体调节BCR信号传导，并受到eb病毒感染的控制。正在进行的研究侧重于BCR内化的机制，以阐明筏和内化之间的确切关系，并揭示这一过程中的调节点。

The B cell antigen receptor (BCR) serves dual, interrelated functions in B cell activation. The first is to initiate signal cascades that result in the transcription of a variety of genes associated with B cell activation. However, signaling through the BCR alone is insufficient for full activation and for this the B cell requires the functions of antigen-specific helper T cells. The interaction of the B and T cells is mediated through the T cells' engagement of antigenic peptide-MHC class II complexes on the B cell surface by the T cell antigen receptor (TCR). The peptide MHC complexes expressed by the B cells are assembled in an intracellular compartment from newly synthesized MHC class II molecules and peptides derived from the antigen bound to the BCR. Our previous studies showed that the BCR transports the antigen to the intracellular compartment where the antigen is degraded and the peptide class II complexes are assembled. The signaling and antigen transport functions of the BCR are interdependent in that the BCR signaling is necessary for the correct and rapid targeting of the antigen to the class II containing compartments. Indeed, for signaling defective BCR antigen is either not processed or the rate of antigen delivery is significantly reduced. In turn, the internalization of the BCR may play an important role in regulating signaling by removing activated receptors from the cell surface. Our recent studies showed that the signaling and antigen targeting functions of the BCR may be coordinated by the BCRs association with cholesterol-rich membrane microdomains termed lipid rafts. We showed that the BCR in resting cells is excluded from rafts that concentrate the Src-family kinase Lyn, required for the initiation of signaling. Following antigen binding the BCR translocates into rafts where it associates with Lyn and signaling is initiated. Subsequently, the BCR is internalized and trafficked to the class II peptide-loading compartment. We learned that the internalization of the receptor is controlled during B cell development, by B cell coreceptors that regulate BCR signaling and by infection by Epstein Barr Virus. Studies in progress are focusing on the mechanism by which the BCR is internalized in order to elucidate the precise relationship between rafts and internalization and to uncover points of regulation in the process.