The RNA-binding protein HuR is required for maintenance of the germinal centre response

Germinal centre (GC) responses may require RNA binding proteins (RBP) for post-transcriptional gene regulation. Here the authors show the RBP HuR supports GCs by promoting Myc and Myc-dependent transcription to enhance antigen-specific GC B cell selection and production of high affinity antibodies. The germinal centre (GC) is required for the generation of high affinity antibodies and immunological memory. Here we show that the RNA binding protein HuR has an essential function in GC B cells to sustain the GC response. In its absence, the GC reaction and production of high-affinity antibody is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively. The expression and splicing patterns of hundreds of genes are altered in the absence of HuR. Among these genes, HuR is required for the expression of Myc and a Myc-dependent transcriptional program that controls GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR regulates the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle, and it modulates a gene signature associated with DNA deamination protecting GC B cells from DNA damage and cell death.

Automated summary

The RNA binding protein HuR plays a crucial role in supporting germinal centre (GC) responses by promoting Myc-dependent transcription and influencing the expression and splicing patterns of genes involved in GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR modulates mRNA splicing and abundance for cell cycle progression, and protects GC B cells from DNA damage and cell death.