Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2019
Erindi/veggspjald / Talk/poster V69
Höfundar / Authors: Kimberley Anderson, Árný Björg Ósvaldsdóttir, Birgit Atzinger, Gunnhildur Ásta Traustadóttir, Aðalheiður Elín Lárusdóttir, Kirstine Nolling Jensen, Jón Þór Bergþórsson, Ingibjörg Harðardóttir, Erna Magnúsdóttir
Starfsvettvangur / Affiliations: Læknadeild Háskóla Íslands
Kynnir / Presenter: Erna Magnúsdóttir
The transcription factor BLIMP1 drives the maturation of naïve-B-cells to become plasma cells, in part by suppressing B-cell immune effector genes. Here we show that BLIMP1 is required for the survival of Waldenström macroglobulinaemia (WM) cells in culture. We further show that BLIMP1 expression is required for the expression of the histone-methyltransferase EZH2. Genome-wide binding and transcriptional profiling show a significant overlap in genes bound and repressed BLIMP1 and EZH2 and their target genes include immune effector molecules such as T-lymphocyte and natural killer (NK) cell ligands. In line with this, we show that in co-culture BLIMP1 knock-down in WM cells leads to an increase in NK cell activation and increased NK cell-mediated cytotoxicity of WM cells. Conversely, EZH2 inhibition leads to an increase in NK cell-mediated WM cell cytotoxicity, showing that the maintenance of EZH2 levels potentially results in WM cell immune evasion.