Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5

Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5
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DOI:
10.1038/ni1100
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发表时间:
2004-09-01
期刊:
影响因子:
30.5
通讯作者:
Cyster, JG
Cyster, JG
中科院分区:
医学1区
文献类型:
--
作者:
Allen, CDC;Ansel, KM;Cyster, JG

文献摘要

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生发中心(GC)暗区和亮区分别隔离经历体细胞超突变和抗原驱动选择的细胞,但指导这种组织的因素尚不清楚。我们在此报告称,趋化因子受体 CXCR4 缺陷的小鼠不存在 GC 组织。中心母细胞高表达 CXCR4,GC B 细胞向 CXCR4 配体 SDF-1 (CXCL12) 迁移,暗区比亮区更丰富。在野生型 GC 的背景下,CXCR4 缺陷细胞被排除在暗区之外。这些发现证实 GC 组织取决于 CXCR4 将中心母细胞分类到暗区。相比之下,CXCR5 有助于将细胞引导至光区,而 CXCL13 的缺陷与异常的光区定位相关。
Germinal center (GC) dark and light zones segregate cells undergoing somatic hypermutation and antigen-driven selection, respectively, yet the factors guiding this organization are unknown. We report here that GC organization was absent from mice deficient in the chemokine receptor CXCR4. Centroblasts had high expression of CXCR4 and GC B cells migrated toward the CXCR4 ligand SDF-1 (CXCL12), which was more abundant in the dark zone than in the light zone. CXCR4-deficient cells were excluded from the dark zone in the context of a wild-type GC. These findings establish that GC organization depends on sorting of centroblasts by CXCR4 into the dark zone. In contrast, CXCR5 helped direct cells to the light zone and deficiency in CXCL13 was associated with aberrant light zone localization.