Plasma Cell Fate is Orchestrated by Large-Scale Changes in Compartmentalization

Plasma cell differentiation is characterized by differentiation of progenitor cells into short-lived and long-lived compartments. Here we examine how gene expression and nuclear architecture are linked to instruct short-lived and long-lived plasma cell fate. We find that plasma cell commitment is concurrent with the nuclear repositioning of transcription start sites associated with activation or repression of genes including the Irf4 and Bcl6 loci, respectively. Intergenic regions associated with the Ebf1 and Prdm1 loci also reposition concomitant with altered patterns of gene expression. Plasma cell differentiation is also enriched for inter-chromosomal associations concurrent at a global scale with alterations in gene expression. Finally, we find that the onset of plasma cell development is associated with a gain in euchromatic strength for genes encoding for cell cycle regulation and DNA repair that characterize in part the long-lived plasma cell fate. We conclude that at the onset of plasma cell development different strategies are applied to modulate genes that dictate short-lived and long-lived plasma cell gene programs.