Séminaire CIRI (02.04.2024) : Sébastien STORCK

Sebastien STORCK, Institut Necker Enfants Malades, INSERM U1151, Paris;  “ DNA methylation and germinal center reaction: what Hells? ”

Abstract: Germinal center is the major source of memory B cells and long-lived plasma cells. Accordingly, the ability to form and maintain germinal centers is key to successful immunization and yet, the factors that dictate their duration and the differentiation into memory B cells and long-lived plasma cells are not fully elucidated. To address this question, we focused on a rare inherited immunodeficiency, the human ICF syndrome (Immunodeficiency, Centromeric Instability and Facial anomalies) caused by loss-of-function mutations in components of DNA methylation pathways (DNMT3B, ZBTB24, CDCA7 and HELLS). We generated an ICF mouse model with a B-cell specific deletion of the chromatin remodeler HELLS, and characterized its phenotype by cytometric, transcriptomic and methyl-seq analyses that revealed the role of HELLS and DNA methylation maintenance in sustaining the germinal center reaction and controlling its output.