Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas

Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas
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DOI:
10.1182/blood-2012-03-415380
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发表时间:
2012-09-13
期刊:
影响因子:
20.3
通讯作者:
Nussenzweig, Michel C.
Nussenzweig, Michel C.
中科院分区:
医学1区
文献类型:
--
作者:
Victora, Gabriel D.;Dominguez-Sola, David;Nussenzweig, Michel C.

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生殖中心(GC)是B细胞克隆扩增、超突变和选择的场所。GC被极化为暗区(DZ)和亮区(LZ),这一区别对GC选择至关重要。然而,人类这些区域中的B细胞之间的差异仍不清楚。我们表明,在小鼠中,CXCR 4和CD 83可用于区分人LZ和DZ细胞。使用这些标志物,我们表明,LZ和DZ细胞在小鼠和人类中的差异,只有在表达的特征“激活”和“增殖”程序,这表明这些人口代表交替状态的单细胞类型,而不是不同的分化阶段。此外,LZ/DZ转录谱显示,除了“分子”伯基特淋巴瘤,几乎所有的人类B细胞恶性肿瘤密切类似LZ细胞,这对我们理解淋巴瘤发生的分子程序具有重要意义。(血。2012;120(11):2240-2248)
Germinal centers (GCs) are sites of B-cell clonal expansion, hypermutation, and selection. GCs are polarized into dark (DZ) and light zones (LZ), a distinction that is of key importance to GC selection. However, the difference between the B cells in each of these zones in humans remains unclear. We show that, as in mice, CXCR4 and CD83 can be used to distinguish human LZ and DZ cells. Using these markers, we show that LZ and DZ cells in mice and humans differ only in the expression of characteristic "activation" and "proliferation" programs, suggesting that these populations represent alternating states of a single-cell type rather than distinct differentiation stages. In addition, LZ/DZ transcriptional profiling shows that, with the exception of "molecular" Burkitt lymphomas, nearly all human B-cell malignancies closely resemble LZ cells, which has important implications for our understanding of the molecular programs of lymphomagenesis. (Blood. 2012;120(11):2240-2248)