Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Cold Spring Harb Perspect Biol. 2010 Jul;2(7):a002295. doi: 10.1101/cshperspect.a002295. Epub 2010 Jun 30.
B-cell responses are initiated by the binding of foreign antigens to the clonally distributed B-cell receptors (BCRs) resulting in the triggering of signaling cascades that activate a variety of genes associated with B-cell activation. Although we now understand the molecular nature of the signaling pathways in considerable detail what remains only poorly understood are the mechanisms by which the information that antigen has bound to the BCR ectodomain is transduced across the B-cell membrane to the BCR cytoplasmic domains to trigger signaling. To a large part this gap in knowledge is because of the paucity of techniques to temporally and spatially resolve changes in the behavior of the BCR that occur within several seconds of antigen binding. With the advent of new live-cell imaging technologies we are gaining our first clear views of the events that lead up to the triggering of BCR signaling cascades. These events may provide potential new targets for therapeutic intervention in disease involving hyper or chronic activation of B cells.
B 细胞反应是由外来抗原与克隆分布的 B 细胞受体(BCR)结合引发的,导致信号级联的触发,从而激活与 B 细胞激活相关的各种基因。尽管我们现在已经相当详细地了解了信号通路的分子性质,但抗原与 BCR 胞外结构域结合的信息如何通过 B 细胞膜转导到 BCR 胞质结构域以触发信号的机制仍知之甚少。在很大程度上,这种知识上的差距是由于缺乏技术来暂时和空间上解决抗原结合后几秒钟内 BCR 行为的变化。随着新的活细胞成像技术的出现,我们正在首次清晰地了解导致 BCR 信号级联触发的事件。这些事件可能为涉及 B 细胞过度或慢性激活的疾病的治疗干预提供潜在的新靶点。