Initiation of cellular organization in lymph nodes is regulated by non-B cell-derived signals and is not dependent on CXC chemokine ligand 13
Initiation of cellular organization in lymph nodes is regulated by non-B cell-derived signals and is not dependent on CXC chemokine ligand 13
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DOI：
10.4049/jimmunol.173.8.4889
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发表时间：
2004-10-15
影响因子：
4.4
通讯作者：
Mebius, RE
中科院分区：
文献类型：
--
作者：
Cupedo, T;Lund, FE;Mebius, RE
在发育中的淋巴结中，启动T和B细胞区形成的分子和细胞事件知之甚少。在这项研究中，我们展示了小鼠新生儿淋巴结样结构的形成经历了一系列不同的阶段。T和B细胞最初的分离是以CXCL13不依赖的方式调节的，特征是第4天B细胞在外皮层以环状模式定位。然而，在这个CXCL13不依赖的淋巴结造模阶段，CXCL13以淋巴毒素-α(1)β(2)(LTalpha(1)β(2))依赖的方式表达和调节。令人惊讶的是，新生儿B细胞不能对这种趋化因子做出反应，也缺乏表面LTalpha(1)β(2)的表达。此时，CD45(+)CD4(+)CD3(-)细胞是主要的LTalpha(1)β(2)表达细胞，也能够对CXCL13做出反应。从第4天开始，结构变化变得依赖于CXCL13，B细胞变得完全对CXCL13有反应，表达LTalpha(1)β(2)，并聚集在解剖上不同的卵泡中。由于CXCL13的初始诱导依赖于LTalpha(1)β(2)，CD45(+)CD4(+)CD3(-)细胞在发育中的淋巴结中诱导趋化因子表达的作用被提出，并因此在微环境形成的启动中发挥作用。
The molecular and cellular events that initiate the formation of T and B cell areas in developing lymph nodes are poorly understood. In this study we show that formation of the lymphoid architecture in murine neonatal lymph nodes evolves through a series of distinct stages. The initial segregation of T and B cells is regulated in a CXCL13-independent manner, characterized by the localization of B cells in a ring-like pattern in the outer cortex on day 4. However, during this CXCL13-independent phase of lymph node modeling, CXCL13 is expressed and regulated in a lymphotoxin-alpha(1)beta(2) (LTalpha(1)beta(2))-dependent manner. Surprisingly, neonatal B cells are unable to respond to this chemokine and also lack surface LTalpha(1)beta(2) expression. At this time, CD45(+)CD4(+)CD3(-) cells are the predominant LTalpha(1)beta(2)-expressing cells and are also capable of responding to CXCL13. From day 4 on, architectural changes become CXCL13 dependent, and B cells become fully CXCL13 responsive, express LTalpha(1)beta(2), and cluster in anatomically distinct follicles. Because the initial induction of CXCL13 is dependent on LTalpha(1)beta(2), a role for CD45(+)CD4(+)CD3(-) cells in inducing chemokine expression in the developing lymph nodes is proposed and, as such, a role in initiation of the shaping of the microenvironment.