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The RNA-binding protein HuR is required for antigen-specific germinal centre B cell selection.

ABSTRACT: The germinal centre (GC) is a hallmark of adaptive immunity. Gene expression in GCs is tightly regulated but the impact of post-transcriptional mechanisms are largely unknown. Here we show that expression of the RNA binding protein HuR is essential in GCs. In its absence, GC B cells are at a competitive disadvantage and high-affinity antibody production is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively to enable the expression of a Myc- dependent transcriptional program essential for light zone B cells to re-enter into the dark zone for further proliferation and Ig somatic hypermutation. HuR controls the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle. HuR modulates a gene signature associated with DNA deamination preserving GC B cells from extensive DNA damage and cell death.

ORGANISM(S): Mus musculus

PROVIDER: GSE145413 | GEO | 2021/09/22

REPOSITORIES: GEO

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2013-11-01 | E-GEOD-49225 | biostudies-arrayexpress

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Project description: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.

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