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

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. Overall design: Germinal centre B cells from the dark zone (DZ, CD19+ IgD- CD38- CD95+ CXCR4+ CD86- cells) and the light zone (LZ, CD19+ IgD- CD38- CD95+ CXCR4- CD86+ cells) were sorted (by FACs) from HuRfl/fl (control) or HuRfl/fl AIDCre (HuR KO) mice at day 7 after immunization with NP-KLH in alum.