Germinal Center Dark Zone harbors ATR-dependent determinants of T-cell exclusion that are also identified in aggressive lymphoma - DLBCLs Cell lines RNA-SEQ project

The germinal center (GC) dark zone (DZ) and light zone (LZ) regions spatially separateexpansion and diversification from selection of antigen-specific B-cells to ensure antibodyaffinity maturation and B cell memory. How GC polarity is established is poorly understood.This study provides novel insights into signals controlling asymmetric T-cell distributionbetween DZ and LZ regions. We identify spatially-resolved DNA damage response andchromatin compaction molecular features precluding DZ T-cell infiltration. The DZ spatialtranscriptional signature linked to T-cell immune evasion clustered aggressive Diffuse LargeB-cell Lymphomas (DLBCL) for differential T cell infiltration. We reveal the dependence ofthe DZ transcriptional core signature on the ATR kinase and dissect its role in restraininginflammatory responses contributing to estabslish an immune-repulsive imprint in DLBCL.These insights may guide ATR-focused treatment strategies bolstering immunotherapy intumors marked by DZ transcriptional and chromatin-associated features.