EIF4A1 is essential in B cells by promoting activation-induced translation

EIF4A1 and cofactors EIF4B and EIF4H have been well characterised in cancers, including B cell malignancies, for their ability to promote the translation of oncogenes with structured 5' untranslated regions but very little is known of their roles in non-malignant cells. Using mouse models to delete Eif4a1, Eif4b or Eif4h in B cells we show that EIF4A1, but not EIF4B or EIF4H, is essential for B cell development and the germinal centre response. Following activation, EIF4A1 facilitates an increased rate of protein synthesis, MYC expression and expression of cell cycle regulators. However, EIF4A1-deficient cells remain viable whereas Hippuristanol treatment induces cell death. Overall design: RNA-seq libraries were prepared from B cells following 24h activation, with four replicates from 8-12-week-old control and Eif4a1 KO mice. Proteomics analysis was also performed from the same samples; data are available using the accession provided in the associated manuscript. Note that replicate 1 for both control and KO were excluded from downstream analysis due to low cell viability following activation.