Abstract
Abstract In order to generate humoral immunity, B cells must differentiate into antibody-secreting cells in response to antigen. LSD1 is a histone demethylase that regulates multiple cellular differentiation pathways and has been implicated to function during B cell differentiation through interaction with Blimp-1. Here we show that LSD1 is necessary for maximal proliferation and differentiation of naïve B cells into LPS-induced plasmablasts. LSD1-deficient B cell differentiation results in the targeted upregulation of hundreds of genes, a subset being Blimp-1 repressed genes, as well as the targeted downregulation of cell cycle genes. Plasmablasts lacking LSD1 fail to close chromatin at naïve B cell active enhancers in addition to PU.1 and IRF4 binding sites. LSD1 directly regulates the Blimp-1 target gene Sell through H3K4me1 demethylation at its Blimp-1 target binding sites. Our data defines LSD1 as a critical transcriptional and epigenetic repressor in plasmablasts.
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