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

• Published in: Cellular & molecular immunology Vol. 20; no. 9; pp. 1063 - 1076
• Main Authors: Osma-Garcia, Ines C, Mouysset, Mailys, Capitan-Sobrino, Dunja, Aubert, Yann, Turner, Martin, Diaz-Muñoz, Manuel D
• Format: Journal Article
• Language: English
• Published: China Nature Publishing Group 20.07.2023; Nature Publishing Group UK
• Subjects: Affinity; Antibiotics; Antibodies; Antigens; Apoptosis; Bone marrow; Cell cycle; Cell differentiation; Clonal selection; Cloning; DNA damage; Flow cytometry; Germinal centers; Lymphocytes B; Mcl-1 protein; Physiology; Positive selection; Post-transcription; Proteins; Proteomes; RNA-binding protein; Transcription activation; Weaning; Cell identity; Adaptive immunity; Post-transcriptional gene regulation; Germinal centers; Apoptosis; RNA binding proteins
• ISSN: 2042-0226; 1672-7681; 2042-0226
• DOI: 10.1038/s41423-023-01063-4

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.