Changes in Chromatin Configuration during Lymphocyte Activation: Unveiling Conserved Molecular Legacies 2117

Abstract Description During an immune response, lymphocytes undergo a dramatic change in chromatin configuration, from a very condensed organization in naïve cells to a decondensed state in activated cells. It has been demonstrated that this change in chromatin architecture is required for αβ T cell proliferation and relies on both intracellular calcium and activation of Protein Kinase C. Given that αβ T cells, B cells, and γδ T cells are derived from a common lymphoid progenitor and utilize similar activation pathways, we hypothesized that chromatin decondensation could similarly regulate their proliferation. To investigate this, we analyzed chromatin status in these cell types from their näive to their activated states. We found that Thy1.2hi (naïve/central memory) γδ T cells possess condensed chromatin in their naïve state, similar to αβ T cells, while B cells and Thy1.2lo (activated/effector memory) γδ T cells have a more open chromatin configuration. To investigate the signaling mechanisms controlling chromatin decondensation in these cells, we interrogated the IP3 and DAG pathways. As previously determined in αβ T cells, we found that intracellular calcium is also necessary for the proper decondensation of chromatin in B cells, Thy1.2hi γδ T cells, and Thy1.2lo γδ T cells. Our data show that these cells utilize conserved signaling pathways differently to decondense chromatin, which may explain the distinct proliferative profiles of these cells in an immune response. Funding Sources Supported by NSF; SC INBRE (NIH); SC Space Grant (NASA); Furman University. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)