Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection.
Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection.
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DOI：
10.1016/j.immuni.2013.08.038
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发表时间：
2013-11-14
期刊：
影响因子：
32.4
通讯作者：
Cyster JG
中科院分区：
文献类型：
--
作者：
Bannard O;Horton RM;Allen CD;An J;Nagasawa T;Cyster JG
生发中心（GC） B细胞在抗体亲和成熟过程中在暗区（DZ）和亮区（LZ）之间循环。这种移动对于GC功能是否必要还没有经过测试。本研究表明，cxcr4缺陷的GC B细胞局限于LZ，逐渐被WT细胞所取代，这表明cxcr4缺陷在DZ通路中起着重要作用。值得注意的是，DZ成中心细胞和LZ成中心细胞表型之间的转变与定位无关。然而，cxcr4缺陷细胞携带较少的突变，并且在CD73+记忆区中过度代表。这些发现与GC B细胞根据定时细胞程序从DZ表型转变为LZ表型的模型一致，但表明DZ细胞的空间分离有助于更有效的突变和选择。最后，我们确定了一个可能支持DZ功能的表达DZ cxcl12的网状细胞网络。在流感诱导的GCs中，缺乏cxcr4的B细胞逐渐被淘汰。根据细胞程序，GC B细胞从DZ状态转变为LZ状态，正常的体细胞高突变率需要进入DZ。DZ包含一个密集的表达cxcl12的网状细胞网络
Germinal center (GC) B cells cycle between the dark zone (DZ) and light zone (LZ) during antibody affinity maturation. Whether this movement is necessary for GC function has not been tested. Here we show that CXCR4-deficient GC B cells, which are restricted to the LZ, are gradually outcompeted by WT cells indicating an essential role for DZ access. Remarkably, the transition between DZ centroblast and LZ centrocyte phenotypes occurred independently of positioning. However, CXCR4-deficient cells carried fewer mutations and were overrepresented in the CD73+ memory compartment. These findings are consistent with a model where GC B cells change from DZ to LZ phenotype according to a timed cellular program but suggest that spatial separation of DZ cells facilitates more effective rounds of mutation and selection. Finally, we identify a network of DZ CXCL12-expressing reticular cells that likely support DZ functions. CXCR4-deficient B cells are gradually outcompeted of influenza-induced GCs GC B cells transition from the DZ to LZ state according to a cellular program DZ access is required for normal somatic hypermutation rates The DZ contains a dense network of CXCL12-expressing reticular cells
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DOI：
10.1084/jem.20111449
发表时间：
2011-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Wang X;Cho B;Suzuki K;Xu Y;Green JA;An J;Cyster JG
通讯作者：
Cyster JG
影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
DOI：
10.1084/jem.20062571
发表时间：
2007-09-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Anderson SM;Tomayko MM;Ahuja A;Haberman AM;Shlomchik MJ
通讯作者：
Shlomchik MJ
影响因子：
64.5
作者：
Victora, Gabriel D.;Schwickert, Tanja A.;Nussenzweig, Michel C.
通讯作者：
Nussenzweig, Michel C.
DOI：
10.1084/jem.194.1.45
发表时间：
2001-07-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hargreaves DC;Hyman PL;Lu TT;Ngo VN;Bidgol A;Suzuki G;Zou YR;Littman DR;Cyster JG
通讯作者：
Cyster JG