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

Ines C. Osma-Garcia, Dunja Capitan-Sobrino, Mailys Mouysset, Sarah E. Bell, Manuel Lebeurrier, Martin Turner () and Manuel D. Diaz-Muñoz ()
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Ines C. Osma-Garcia: University Paul Sabatier, CHU Purpan
Dunja Capitan-Sobrino: University Paul Sabatier, CHU Purpan
Mailys Mouysset: University Paul Sabatier, CHU Purpan
Sarah E. Bell: The Babraham Institute
Manuel Lebeurrier: University Paul Sabatier, CHU Purpan
Martin Turner: The Babraham Institute
Manuel D. Diaz-Muñoz: University Paul Sabatier, CHU Purpan

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-26908-2

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