RORα plays an important role in generation and maintenance of memory B cells

Abstract Memory B cells (MBCs) are antigen-specific and long-lived. Upon reactivation, they can differentiate into plasma to secrete large amounts of high-affinity mostly class-switched antibodies. Prompted by our integrative analysis the human MBC transcriptome chromatin landscape which redundantly identified transcriptional factor RORα as central identity (sw)MBCs, we investigated contribution generation maintenance MBCs. We found that is selectively expressed at a high level in both mouse swMBCs. then constructed genetically modified AicdacreRorafl/flmice, specifically deleted activated undergoing class switching. immunization with NP-CGG, AicdacreRorafl/flmice significantly reduced NP-specific swMBCs part primary response otherwise without perturbation germinal center formation, class-switch DNA recombination, somatic hypermutation or cell differentiation, but leading defective anamnestic anti-NP-antibody response. To define role maintenance, generated tamoxifen-inducible conditional knockout CD19cre/ERT2Rorafl/flmice, could be ablated already NP-CGG. ablation led loss anti-NP-response. Thus, plays an important not only also Further mechanistic insight swMBC will provided Cut&Tag RNA-Seq experiments identify sites enrichment across genome targets Supported NIH grants AI 079705, 105813, 167416 LRA grant 641363 PC.