A coordinated change in chemokine responsiveness guides plasma cell movements.
A coordinated change in chemokine responsiveness guides plasma cell movements.
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DOI：
10.1084/jem.194.1.45
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发表时间：
2001-07-02
期刊：
影响因子：
--
通讯作者：
Cyster JG
中科院分区：
文献类型：
--
作者：
Hargreaves DC;Hyman PL;Lu TT;Ngo VN;Bidgol A;Suzuki G;Zou YR;Littman DR;Cyster JG
分泌抗体的浆细胞是非再循环的，并停留在脾红髓、淋巴结髓索和骨髓中。调节浆细胞定位的因素定义不清。在这里，我们证明，与它们的B细胞前体相比，浆细胞表现出增加的趋化敏感性CXCR 4配体CXCL 12。同时，它们下调CXCR 5和CCR 7，并降低对B和T区趋化因子CXCL 13、CCL 19和CCL 21的反应性。我们证明CXCL12在脾红髓和淋巴结髓索以及骨髓中表达。在用CXCR4缺陷胎肝细胞重建的嵌合小鼠中，浆细胞错误定位在脾脏中，在血液中发现数量增加，并且不能在骨髓中正常积累。我们的研究结果表明，随着B细胞分化为浆细胞，它们经历了趋化因子反应性的协调变化，该趋化因子反应性调节它们在次级淋巴器官中的运动并促进在骨髓内的沉积。
Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.
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