Control of plasma cell formation by chromatin remodelers and post transcriptional RNA regulation

Over the course of differentiation into antibody-forming plasma cells that secrete vast amounts of antibodies over a long period of time, B lymphocytes undergo dramatic transcriptional changes. The B lymphocyte to plasma cell transformation depends on chromatin landscape changes; however, the mechanism by which specific chromatin remodelers facilitate and maintain the commitment to the plasma cell lineage is unknown. To address this problem, we combine a series of new, informative animal models with advanced mechanistic analyses of chromatin modulator functions. Specifically, we focus on the role of the mammalian ATP-dependent chromatin remodeling complexes in B cell differentiation into antibody-forming cells in vivo. We dissect the mechanism of each chromatin remodeler by defining the subunit and associated factor composition and chromatin targeting of each complex over the course of differentiation. We plan to examine these mechanistic findings in healthy and malignant human B cells.