The RNA binding proteins TIA1 and TIAL1 protect germinal centre responses from apoptosis [iCLIP]
Germinal centres (GC) are essential for the establishment of long-lasting antibody responses. In there, GC B cells rely on post-transcriptional RNA mechanisms for translating activation-associated transcriptional programs into functional changes in the cell proteome. However, we still lack knowledge about which are the critical proteins driving these key mechanisms. 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 pro-survival molecule MCL1. Altogether, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells. Overall design: Individual cross-linking immunoprecipitation (iCLIP) and sequencing for TIA1 and TIAL1 in follicular B cells isolated from the spleen of C57BL/6 mice and stimulated with anti-IgM, anti-CD40 and rmIL4 for 48h.