The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis

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外文摘要：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.

外文关键词：

Adaptive immunityGerminal centersPost-transcriptional gene regulationRNA binding proteinsCell identityApoptosis

作者：

Ines C.Osma-Garcia、Mailys Mouysset、Dunja Capitan-Sobrino、Yann Aubert、Martin Turner、Manuel D.Diaz-Mu?oz

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作者单位：

Toulouse Institute for Infectious and Inflammatory Diseases(INFINITy),Inserm UMR1291,CNRS UMR5051,University Paul Sabatier,CHU Purpan,Toulouse 31024,France

Immunology Program,The Babraham Institute,Cambridge,UK

基金：

ATIP-Avenir-Plan CancerANRfoundation ARSEPfoundation ARCLa Ligue Contre Le CancerINSPIRE(Region Occitanie,Inserm and CHU Toulouse)a BBSRC core funding granta Wellcome Investigator awardBoehringer Ingelheim Fonds

项目编号：

C18003BSANR-20-CE15-0007R19201BB200823/Z/16/Z

出版年：

2023

DOI：

10.1038/s41423-023-01063-4

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(9)

参考文献量68