| First Author | Haines RR | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 9 | Pages | 2799-2811 |
| PubMed ID | 30232138 | Mgi Jnum | J:267728 |
| Mgi Id | MGI:6258100 | Doi | 10.4049/jimmunol.1800952 |
| Citation | Haines RR, et al. (2018) The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast Differentiation. J Immunol 201(9):2799-2811 |
| abstractText | B cells undergo epigenetic remodeling as they differentiate into Ab-secreting cells (ASC). LSD1 is a histone demethylase known to decommission active enhancers and cooperate with the ASC master regulatory transcription factor Blimp-1. The contribution of LSD1 to ASC formation is poorly understood. In this study, we show that LSD1 is necessary for proliferation and differentiation of mouse naive B cells (nB) into plasmablasts (PB). Following LPS inoculation, LSD1-deficient hosts exhibited a 2-fold reduction of splenic PB and serum IgM. LSD1-deficient PB exhibited derepression and superinduction of genes involved in immune system processes; a subset of these being direct Blimp-1 target-repressed genes. Cell cycle genes were globally downregulated without LSD1, which corresponded to a decrease in the proliferative capacity of LSD1-deficient activated B cells. PB lacking LSD1 displayed increased histone H3 lysine 4 monomethylation and chromatin accessibility at nB active enhancers and the binding sites of transcription factors Blimp-1, PU.1, and IRF4 that mapped to LSD1-repressed genes. Together, these data show that LSD1 is required for normal in vivo PB formation, distinguish LSD1 as a transcriptional rheostat and epigenetic modifier of B cell differentiation, and identify LSD1 as a factor responsible for decommissioning nB active enhancers. |
