A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival.
A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival.
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DOI：
10.1084/jem.20091489
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发表时间：
2010-04-12
期刊：
影响因子：
--
通讯作者：
Tybulewicz VL
中科院分区：
文献类型：
--
作者：
Henderson RB;Grys K;Vehlow A;de Bettignies C;Zachacz A;Henley T;Turner M;Batista F;Tybulewicz VL
Rac 1和Rac 2 GTP酶抑制来自多种受体的信号，导致细胞迁移、粘附、增殖和存活。在不存在Rac 1和Rac 2的情况下，B细胞发育在IgD-过渡型B细胞阶段被阻止，我们称之为过渡型0（T0）。我们发现，T0细胞不能进入脾的白色髓，直到它们成熟到T1和T2阶段，并且这种进入白色髓需要整合素和趋化因子受体信号传导，并且是细胞存活所必需的。在缺乏Rac 1和Rac 2的情况下，过渡性B细胞不能响应趋化因子而迁移，并且不能进入脾白色髓。我们认为Rac 1和Rac 2的缺失导致T0期的阻滞至少部分是因为过渡期的B细胞需要迁移到白色牙髓中以接收生存信号。最后，我们表明，在没有Syk，一种激酶，转导B细胞抗原受体信号所需的积极选择，发展被逮捕在相同的T0阶段，过渡B细胞排除在白色纸浆。因此，这些研究鉴定了与B细胞正选择一致的新的发育检查点。
Rac1 and Rac2 GTPases transduce signals from multiple receptors leading to cell migration, adhesion, proliferation, and survival. In the absence of Rac1 and Rac2, B cell development is arrested at an IgD− transitional B cell stage that we term transitional type 0 (T0). We show that T0 cells cannot enter the white pulp of the spleen until they mature into the T1 and T2 stages, and that this entry into the white pulp requires integrin and chemokine receptor signaling and is required for cell survival. In the absence of Rac1 and Rac2, transitional B cells are unable to migrate in response to chemokines and cannot enter the splenic white pulp. We propose that loss of Rac1 and Rac2 causes arrest at the T0 stage at least in part because transitional B cells need to migrate into the white pulp to receive survival signals. Finally, we show that in the absence of Syk, a kinase that transduces B cell antigen receptor signals required for positive selection, development is arrested at the same T0 stage, with transitional B cells excluded from the white pulp. Thus, these studies identify a novel developmental checkpoint that coincides with B cell positive selection.
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脾脏中的B细胞发育发生在离散的步骤中，并取决于B细胞受体衍生的信号的质量。
影响因子：
15.3
作者：
Loder, F;Mutschler, B;Ray, R J;Paige, C J;Sideras, P;Torres, R;Lamers, M C;Carsetti, R
通讯作者：
Carsetti, R
影响因子：
15.3
作者：
Fujikawa, K;Miletic, AV;Alt, FW;Faccio, R;Brown, T;Hoog, J;Fredericks, J;Nishi, S;Mildiner, S;Moores, SL;Brugge, J;Rosen, FS;Swat, W
通讯作者：
Swat, W
影响因子：
15.3
作者：
Bowman, E P;Campbell, J J;Soler, D;Dong, Z;Manlongat, N;Picarella, D;Hardy, R R;Butcher, E C
通讯作者：
Butcher, E C
影响因子：
20.3
作者：
Cariappa, Annaiah;Chase, Catharine;Pillai, Shiv
通讯作者：
Pillai, Shiv
影响因子：
20.3
作者：
Lindsley, Robert Coleman;Thomas, Matthew;Allman, David
通讯作者：
Allman, David