Mechanisms of Activation-Induced Chromatin Decondensation in the Lymphoid Lineage

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Abstract During an immune response, αβ T cells undergo a dramatic change in chromatin configuration, from a very condensed organization seen in naïve cells to a decondensed state in activated cells. It has previously been demonstrated that this change in chromatin architecture is required for αβ T cell proliferation. Since B cells and γδ T cells share the same lineage as αβ T cells, originating from a common lymphoid progenitor, we hypothesized that chromatin status could regulate their proliferation as well. To test this hypothesis, we analyzed chromatin status as a function of activation and found that in their basal (naïve) state, both B cells and Thy1.2hi (naïve) γδ T cells possess condensed chromatin, similar to αβ T cells, whereas Thy1.2lo (activated/memory) γδ T cells have a more open chromatin configuration. Upon exposure to activation stimuli, all three cell types decondense chromatin, but to different extents that correlate with their known ability to proliferate in response to activation stimuli. To investigate the signaling mechanisms controlling chromatin decondensation in these cells, we selectively activated the IP3 and DAG pathways, demonstrating that activation of either pathway can induce the decondensation of chromatin. Investigating the IP3 pathway further, we show that in B cells, the flux of intracellular calcium is required for the proper decondensation of chromatin, similar to previously published data on αβ T cells. Future studies will investigate if intracellular calcium is sufficient for chromatin decondensation in γδ T cells, establishing a conserved mechanism to control proliferation of cells of the lymphoid lineage during an immune response.