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 funct...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.展开更多
基金We thank all personnel from the Toulouse animal facility CREFRE and from the flow cytometry,imaging,transcriptomics and bioinformatics technical platforms of INFINITy.M.D.D-M.is supported by ATIP-Avenir-Plan Cancer(C18003BS),ANR(ANR-20-CE15-0007)foundation ARSEP R19201BB,foundation ARC,La Ligue Contre Le Cancer and INSPIRE(Region Occitanie,Inserm and CHU Toulouse)M.T.is supported with a BBSRC core funding grant and a Wellcome Investigator award(200823/Z/16/Z).D.C.-S.is supported by Boehringer Ingelheim Fonds.
文摘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.
