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      Intracellular BH3 profiling reveals shifts in anti-apoptotic dependency in B-cell maturation and activation

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      bioRxiv

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          Abstract

          Apoptosis is critical to B-cell maturation, but studies of apoptotic regulation in primary human B cells is lacking. Previously, we found that infecting human B cells with Epstein-Barr virus induces two different survival strategies (Price et al. , 2017). Here, we sought to better understand the mechanisms of apoptotic regulation in normal and activated B cells. Using intracellular BH3 profiling (iBH3), we defined the Bcl2-dependency of B-cell subsets from human peripheral blood and tonsillar lymphoid tissue as well as mitogen-activated B cells. We found that naïve and memory B cells were BCL-2 dependent, while germinal center B cells were MCL-1 dependent and plasma cells were BCL-XL dependent. Proliferating B cells activated by CpG or CD40L/IL-4 became more dependent upon MCL-1 and BCL-XL. As B-cell lymphomas often rely on survival mechanisms derived from normal and activated B cells, these findings offer new insight into potential therapeutic strategies for lymphomas.

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          Author and article information

          Journal
          bioRxiv
          June 09 2017
          Article
          10.1101/148437
          b898b40a-c220-4982-a2f2-5fd909182eea
          © 2017
          History

          Molecular biology,Microscopy & Imaging
          Molecular biology, Microscopy & Imaging

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