RNA helicase DHX29 controls the translation of transcription factors involved in germinal center response and plasma cell differentiation in mice.

The roles of translational control in the immune system are incompletely understood. Using a CRISPR/Cas9-mediated functional screen of RNA helicases in an in vitro system of plasma cell differentiation, we identify in this study DHX29 as a critical regulator of this process. Mice with B-cell-specific deletion of Dhx29 exhibit severely impaired germinal center B-cell formation, plasma cell differentiation, and antibody production. Mechanistically, DHX29 promotes translation of Tcf3 and Tle3 mRNAs via binding to their 5' untranslated regions (UTRs). In the absence of DHX29, B cells exhibit normal proliferation but fail to undergo class switch to IgG1 and differentiation into plasma cells, resulting in impaired antibody production. Ectopic expression of TCF3 and TLE3 largely restores plasma cell differentiation of Dhx29-deficient B cells. Our study provides insights into the functional importance of translational control in the immune system by unraveling critical roles of the RNA helicase DHX29 in the translation of key transcription factors controlling germinal center response and plasma cell differentiation.