Heme augments proliferation and epigenetic programming during B cell differentiation

Abstract Heme is an iron-containing porphyrin ring that a key part of the cytochrome proteins function in electron transport chain and facilitate OXPHOS metabolism. Recently, our group found many iron-metabolism related genes are highly expressed B cells, particularly memory cells (MBC) both mice humans. In ex vivo cultures, naïve (nB) MBC respond to heme addition by augmenting frequency plasmablast formation. this work, we further characterized role cell differentiation function. To begin addressing question how modulates differentiation, proliferation, or both, first conducted cultures CellTraceYellow (CTY)-labeled stimulated with CD40, IL-4 IL-5, treated without heme. We division occurs within 28 hours post-stimulation for nB were divide earlier than those vehicle.. When number each was analyzed, more later divisions heme-treated vehicle-treated ones, suggesting important proliferation. characterize molecular effects on preformed RNA-seq ATAC-seq activated plasmablasts. The augmented accessible chromatin gene expression hundreds leading differences surrounding metabolic regulators. These data understanding promotes formation antibody secreting