Wienands J
Institute of Biology III, University of Freiburg and Max-Planck-Institute of Immunobiology, Germany.
Immunobiology. 2000 Aug;202(2):120-33. doi: 10.1016/S0171-2985(00)80059-5.
The primary function of B lymphocytes is to contribute to the elimination of foreign antigens by producing large amounts of soluble antibodies. The activation of B cells through their antigen receptor triggers a dynamic network of intracellular signaling proteins. The recent identification of the cytoplasmic adaptor protein SLP-65 (also called BLNK or BASH) provided insight in how the antigen receptor-regulated protein tyrosine kinases couple to downstream signaling cascades, including the mobilization of Ca2+ ions, activation of mitogen-activated kinases and reorganization of the cytoskeleton architecture. While these events have been mostly studied in mature B cells, it is now clear that the components of the antigen receptor and its downstream effector elements play also a central role during early and late B cell development, and in the apoptotic elimination of B cells with reactivity to self-antigens. Thus, genetic defects affecting the expression of antigen receptor subunits or its intracellular signaling proteins can interfere with B cell development and activation, and can cause severe antibody deficiencies in mouse and man. In this article I summarize our current picture of the B cell antigen receptor, how the extracellular signal is transported into the cell interior, and how dysregulation of these processes contribute to immune defects.
B淋巴细胞的主要功能是通过产生大量可溶性抗体来促进对外源抗原的清除。B细胞通过其抗原受体的激活触发了细胞内信号蛋白的动态网络。最近对细胞质衔接蛋白SLP-65（也称为BLNK或BASH）的鉴定，为抗原受体调节的蛋白酪氨酸激酶如何与下游信号级联反应偶联提供了见解，这些下游信号级联反应包括钙离子的动员、丝裂原活化激酶的激活以及细胞骨架结构的重组。虽然这些事件大多在成熟B细胞中进行了研究，但现在很清楚，抗原受体及其下游效应元件的组成部分在B细胞早期和晚期发育过程中以及在对自身抗原有反应性的B细胞的凋亡清除中也起着核心作用。因此，影响抗原受体亚基或其细胞内信号蛋白表达的遗传缺陷会干扰B细胞的发育和激活，并可在小鼠和人类中导致严重的抗体缺陷。在本文中，我总结了我们目前对B细胞抗原受体的认识，细胞外信号如何传递到细胞内部，以及这些过程的失调如何导致免疫缺陷。
