RIF1 acts as a gatekeeper of B cell identity during late differentiation

RIF1 is a multifunctional protein that promotes immunoglobulin (Ig) isotype diversification. Whether RIF1 plays additional roles in adaptive immunity is unknown. In this study, we observed an upregulation of RIF1 expression following mature B cell activation, while its deficiency led to a deregulated expression profile enriched in genes typically expressed in B cell progenitors and plasma cells (PC). RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into PC upon immunization. Therefore, RIF1 serves as a cell identity gatekeeper during late B cell differentiation, providing an additional layer of control in the establishment of humoral immunity. Overall design: To elucidate the role of RIF1 in B-cell development and plasma blast differentiation, we extracted spleenocytes from CD19 Cre/+ mice and Rif1 F/F CD19 Cre/+ mice. Following isolation, these cells were stimulated with a cytokine-LPS cocktail, and subsequently harvested at 48, 72, and 96-hour intervals post-activation. To gain an in-depth understanding and to make a comprehensive comparison of the gene expression profiles, the samples were subjected to analysis via next-generation sequencing.