S1P1 receptor directs the release of immature B cells from bone marrow into blood.
S1P1 receptor directs the release of immature B cells from bone marrow into blood.
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DOI：
10.1084/jem.20092210
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发表时间：
2010-05-10
期刊：
影响因子：
--
通讯作者：
Proia RL
中科院分区：
文献类型：
--
作者：
Allende ML;Tuymetova G;Lee BG;Bonifacino E;Wu YP;Proia RL
S1 P1受体表达是新形成的T细胞从胸腺排出以及成熟的T和B细胞从次级淋巴器官排出所必需的。在这项研究中，我们删除了在发育中的B细胞在骨髓中的S1 P1受体基因（S1 pr 1）的表达。尽管在B细胞特异性S1 pr 1敲除（B-S1 pr 1 KO）小鼠中骨髓内的B细胞成熟基本正常，但与对照小鼠相比，它们的新产生的未成熟B细胞以异常低的数量出现在血液中。在B-S1 pr 1 KO小鼠的骨髓中，与对照小鼠相比，与血管隔室接触的未成熟B细胞显示出增加的凋亡。在发育中的骨髓B细胞中，CD 69（S1 P1受体表达的负调节因子）的强制表达也减少了血液中未成熟B细胞的数量。CXCR 4信号传导的减弱是发育中的B细胞在骨髓中适当保留所必需的，但并不像对照小鼠那样有效地将未成熟的B细胞释放到B-S1 pr 1 KO小鼠的血液中。我们的研究结果表明，S1 P1受体提供了一个必要的信号，新产生的未成熟B细胞从骨髓到血液的有效转移。
S1P1 receptor expression is required for the egress of newly formed T cells from the thymus and exit of mature T and B cells from secondary lymphoid organs. In this study, we deleted the expression of the S1P1 receptor gene (S1pr1) in developing B cells in the bone marrow. Although B cell maturation within the bone marrow was largely normal in the B cell–specific S1pr1 knockout (B-S1pr1KO) mice, their newly generated immature B cells appeared in the blood at abnormally low numbers as compared with control mice. In the bone marrow of B-S1pr1KO mice, immature B cells in contact with the vascular compartment displayed increased apoptosis as compared with control mice. Forced expression of CD69, a negative regulator of S1P1 receptor expression, in developing bone marrow B cells also reduced the number of immature B cells in the blood. Attenuation of CXCR4 signaling, which is required for the proper retention of developing B cells in bone marrow, did not release immature B cells into the blood of B-S1pr1KO mice as effectively as in control mice. Our results indicate that the S1P1 receptor provides a signal necessary for the efficient transfer of newly generated immature B cells from the bone marrow to the blood.
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