Table_3_Pseudotemporal ordering of spatial lymphoid tissue microenvironment profiles trails Unclassified DLBCL at the periphery of the follicle.xlsx

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas.

本研究针对反应性淋巴组织内不同微区域的转录特征建立了拟时序排序（pseudotemporal ordering），所涉及的微区域包括生发中心暗区（DZ）、生发中心明区（LZ）以及滤泡周区域（Peri）。本研究借助源自DZ、LZ和Peri功能微环境的拟时轨迹，对弥漫大B细胞淋巴瘤（Diffuse Large B-cell Lymphoma, DLBCL）病例的转录组进行了排序。所得拟时序轨迹的顶点以肿瘤坏死因子受体（TNFR）信号通路介导的分子程序富集以及抑制性免疫检查点过表达为特征，该顶点契合于一种独立的滤泡周生物学表型。该观察结果与富集于未分类/3型细胞起源（Cell of Origin, COO）亚型的DLBCL病例密切相关，由此引发了关于这类特殊病例是否存在生发中心外（extra-GC）微环境印记的诸多疑问。本研究为功能性淋巴组织微环境的转录谱分析与弥漫大B细胞淋巴瘤中不断演进的细胞起源概念之间的关联，提供了颇具启发性的视角。