PDF(Pubmed)
Abstract：
Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.
摘要：
生发中心（GC）对于建立持久的抗体反应至关重要。GCB细胞依靠转录后RNA机制将激活相关的转录程序翻译成细胞蛋白质组中的功能变化。然而,驱动这些关键机制的关键蛋白质仍然未知。这里,我们显示RNA结合蛋白TIA1和TIAL1是产生持久GC反应所必需的。TIA1-和TIAL1缺陷的GCB细胞无法进行抗原介导的阳性选择，扩增并分化为B细胞克隆，产生高亲和力抗体。机械上,TIA1和TIAL1控制暗区和亮区GCB细胞的转录身份，并能够及时表达前存活分子MCL1。因此，我们在此证明TIA1和TIAL1是选择高亲和力抗原特异性GCB细胞的转录后程序中的关键参与者。
