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Novel specialized cell state and spatial compartments within the germinal center.
Nature Immunology ( IF 27.7 ) Pub Date : 2020-04-27 , DOI: 10.1038/s41590-020-0660-2
Domenick E Kennedy 1 , Michael K Okoreeh 1 , Mark Maienschein-Cline 2 , Junting Ai 1 , Margaret Veselits 1 , Kaitlin C McLean 1 , Yogesh Dhungana 3 , Hong Wang 4, 5 , Junmin Peng 4, 5 , Hongbo Chi 3 , Malay Mandal 1 , Marcus R Clark 1
Affiliation  

Within germinal centers (GCs), complex and highly orchestrated molecular programs must balance proliferation, somatic hypermutation and selection to both provide effective humoral immunity and to protect against genomic instability and neoplastic transformation. In contrast to this complexity, GC B cells are canonically divided into two principal populations, dark zone (DZ) and light zone (LZ) cells. We now demonstrate that, following selection in the LZ, B cells migrated to specialized sites within the canonical DZ that contained tingible body macrophages and were sites of ongoing cell division. Proliferating DZ (DZp) cells then transited into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. Multidimensional analysis revealed distinct molecular programs in each population commensurate with observed compartmentalization of noncompatible functions. These data provide a new three-cell population model that both orders critical GC functions and reveals essential molecular programs of humoral adaptive immunity.

中文翻译:

生发中心内的新型特殊细胞状态和空间区室。

在生发中心(GC)中,复杂且高度协调的分子程序必须平衡增殖,体细胞超突变和选择,以提供有效的体液免疫力并防止基因组不稳定和肿瘤转化。与这种复杂性相反,GC B细胞被规范地分为两个主要种群,暗区(DZ)和亮区(LZ)细胞。我们现在证明,在LZ中进行选择后,B细胞迁移到规范DZ中的特定位点,该DZ包含可识别的身体巨噬细胞,并且是正在进行细胞分裂的位点。然后,增殖的DZ(DZp)细胞过渡到较大的DZ中,成为分化DZ(DZd)细胞,然后重新进入LZ。多维分析显示每个人口中不同的分子程序,与观察到的不兼容功能区分开。这些数据提供了一个新的三细胞种群模型,该模型既订购了重要的GC功能,又揭示了体液适应性免疫的基本分子程序。
更新日期:2020-04-27
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