Translational control of germinal center response and plasma cell differentiation by RNA helicase Dhx29 [CUT&Tag]

The roles of translational control in the immune system are poorly understood. In this study, we performed CRISPR/Cas9-mediated functional screening of RNA helicases in an in vitro system of plasma cell differentiation and identified Dhx29 as a critical regulator of this process. Mice with B cell-specific deletion of Dhx29 exhibited severely impaired germinal center B cell formation, plasma cell differentiation, and antibody production. Mechanistically, Dhx29 promotes translation of Tcf3 and Tle3 via binding to 5’UTRs of those mRNAs. 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. Therefore, this study unravels critical roles of Dhx29 in promoting translation of key transcription factors controlling germinal center response and plasma cell differentiation, discovers a previously unrecognized role of Tle3 in plasma cell differentiation, and illustrates the functional importance of translation control in the immune system.