BAFF mediates survival of peripheral immature B lymphocytes.
BAFF mediates survival of peripheral immature B lymphocytes.
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DOI：
10.1084/jem.192.10.1453
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发表时间：
2000-11-20
期刊：
影响因子：
--
通讯作者：
Mackay F
中科院分区：
文献类型：
--
作者：
Batten M;Groom J;Cachero TG;Qian F;Schneider P;Tschopp J;Browning JL;Mackay F
B细胞成熟是一个非常有选择性的过程，需要精细调节的分化和存活信号。来自TNF家族的B细胞活化因子（BAFF）是结合B细胞并增强B细胞受体（BCR）介导的增殖的TNF家族成员。BAFF在B细胞存活中的作用通过观察到用阻断BAFF的试剂处理的小鼠中外周B细胞数量减少以及在来自BAFF转基因（Tg）小鼠的B细胞中检测到高Bcl-2水平而得到证实。我们在体外测试了BAFF对来自初级和次级淋巴器官的淋巴细胞的存活效果。BAFF诱导脾未成熟B细胞亚群的存活，称为过渡型2（T2）B细胞。BAFF处理允许T2 B细胞存活并响应于通过BCR的信号而分化成成熟B细胞。在BAFF Tg小鼠中，T2和边缘区（MZ）B细胞隔室特别增大。不成熟的过渡性B细胞是负选择的目标，负选择被认为是促进自身耐受的特征。这些发现支持了一个模型，其中过多的BAFF介导的外周未成熟B细胞的存活有助于自身反应性B细胞的出现和成熟，偏向于MZ区室。本研究为B细胞成熟和耐受的调控机制提供了新的线索。
B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. B cell activation factor from the TNF family (BAFF) is a TNF family member that binds to B cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in B cell survival was suggested by the observation of reduced peripheral B cell numbers in mice treated with reagents blocking BAFF, and high Bcl-2 levels detected in B cells from BAFF transgenic (Tg) mice. We tested in vitro the survival effect of BAFF on lymphocytes derived from primary and secondary lymphoid organs. BAFF induced survival of a subset of splenic immature B cells, referred to as transitional type 2 (T2) B cells. BAFF treatment allowed T2 B cells to survive and differentiate into mature B cells in response to signals through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. Immature transitional B cells are targets for negative selection, a feature thought to promote self-tolerance. These findings support a model in which excessive BAFF-mediated survival of peripheral immature B cells contributes to the emergence and maturation of autoreactive B cells, skewed towards the MZ compartment. This work provides new clues on mechanisms regulating B cell maturation and tolerance.
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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：
5.4
作者：
LIU, YJ;OLDFIELD, S;MACLENNAN, ICM
通讯作者：
MACLENNAN, ICM
影响因子：
11.4
作者：
LAABI, Y;GRAS, MP;TSAPIS, A
通讯作者：
TSAPIS, A
影响因子：
4.4
作者：
GRAS, MP;LAABI, Y;TSAPIS, A
通讯作者：
TSAPIS, A
影响因子：
30.5
作者：
Guinamard, R;Okigaki, M;Ravetch, JV
通讯作者：
Ravetch, JV