Kinetic modeling reveals a common death niche for newly formed and mature B cells.
Kinetic modeling reveals a common death niche for newly formed and mature B cells.
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DOI：
10.1371/journal.pone.0009497
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发表时间：
2010-03-02
期刊：
影响因子：
3.7
通讯作者：
Mehr R
中科院分区：
文献类型：
--
作者：
Shahaf G;Cancro MP;Mehr R
B淋巴细胞在缺乏适当的第二信号的情况下，在强BCR连接后被消除，并且这种机制介导了骨髓和外周中晚期分化步骤期间的大量细胞损失。成熟的B细胞也可以通过这种机制以及通过正常的更新而被消除，但是尚未鉴定出含有注定要被消除的成熟细胞的群体。在此，我们询问过渡期3（T3）亚群，其中包含大多数新形成的细胞经历无反应性死亡，是否也可能包括成熟的B细胞注定消除。为了询问这一假设及其影响，我们将数学模型应用于先前生成的体内标记数据。我们的分析表明，T3 B细胞的死亡率远远高于所有其他脾B细胞亚群的死亡率。此外，该模型中，T3池包括新形成的和成熟的原代B细胞注定凋亡死亡，表明这种细胞损失可能占几乎所有的成熟B细胞更新。这一发现对正常成熟B细胞更新的机制有意义。
B lymphocytes are subject to elimination following strong BCR ligation in the absence of appropriate second signals, and this mechanism mediates substantial cell losses during late differentiation steps in the bone marrow and periphery. Mature B cells may also be eliminated through this mechanism as well as through normal turnover, but the population containing mature cells destined for elimination has not been identified. Herein, we asked whether the transitional 3 (T3) subset, which contains most newly formed cells undergoing anergic death, could also include mature B cells destined for elimination. To interrogate this hypothesis and its implications, we applied mathematical models to previously generated in vivo labeling data. Our analyses reveal that the death rate of T3 B cells is far higher than the death rates of all other splenic B cell subpopulations. Further, the model, in which the T3 pool includes both newly formed and mature primary B cells destined for apoptotic death, shows that this cell loss may account for nearly all mature B cell turnover. This finding has implications for the mechanism of normal mature B cell turnover.
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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：
4.4
作者：
Monroe, JG;Bannish, G;Sater, R
通讯作者：
Sater, R
影响因子：
3.5
作者：
Gorfine, M;Freedman, L;Mehr, R
通讯作者：
Mehr, R
影响因子：
64.8
作者：
GOODNOW, CC;CROSBIE, J;BASTEN, A
通讯作者：
BASTEN, A
影响因子：
64.8
作者：
NEMAZEE, DA;BURKI, K
通讯作者：
BURKI, K