The RNA binding proteins TIA1 and TIAL1 protect germinal centre responses from apoptosis

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. Splenic germinal centre B cells from the dark zone (DZ) and the light zone (LZ) were sorted (by FACs) from Tia1fl/fl Tial1fl/fl (control) or Tia1fl/fl Tial1fl/fl AIDCre (Tia1 Tial1 double KO) mice at day 7 after immunization (ip) with NP-KLH in alum.