Cutting edge: Acute and chronic exposure of immature B cells to antigen leads to impaired homing and SHIP1-dependent reduction in stromal cell-derived factor-1 responsiveness
Cutting edge: Acute and chronic exposure of immature B cells to antigen leads to impaired homing and SHIP1-dependent reduction in stromal cell-derived factor-1 responsiveness
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DOI：
10.4049/jimmunol.178.6.3353
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Cambier, John C.
中科院分区：
文献类型：
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作者：
Brauweiler, Anne;Merrell, Kevin;Cambier, John C.
B细胞与外周中同源自身Ag的相遇可导致无反应性，这种状况的特征在于解剖定位改变、寿命缩短和对Ag刺激的不敏感性。我们最近报道，一个未成熟的B细胞遇到同源自身抗原在骨髓中也可以导致无反应性。在这项研究中，我们表明，无反应性以及急性银刺激的未成熟B细胞是有缺陷的基质细胞衍生因子-1（SDF-1）诱导的钙动员和迁移，并不本地化的骨髓过继转移。这种低反应性不涉及CXCR 4调节。然而，BCR信号介导的对SDF-1的低反应性与5-肌醇磷酸酶SHIP 1的磷酸化有关，并且需要SHIP 1表达。因此，与同源抗原的接触可能通过阻止SDF-1诱导的磷脂酰肌醇3，4，5-三磷酸的积累，触发未成熟B细胞从骨髓中过早移出。
An encounter of B cells with cognate self Ags in the periphery can lead to anergy, a condition characterized by altered anatomical localization, shortened life span, and refractility to Ag stimulation. We recently reported that an immature B cell encounter with cognate self-Ag in the bone marrow can also lead to anergy. In this study we show that anergic as well as acutely Ag-stimulated immature B cells are defective in stromal cell-derived factor-1 (SDF-1)-induced calcium mobilization and migration and do not localize to bone marrow following adoptive transfer. This hyporesponsiveness does not involve CXCR4 modulation. However, BCR signal-mediated hyporesponsiveness to SDF-1 is associated with phosphorylation of the 5-inositol phosphatase SHIP1 and requires SHIP1 expression. Therefore, an encounter with cognateAg may, by preventing SDF-1-induced phosphatidylinositol 3,4,5-triphosphate accumulation, trigger premature emigration of immature B cells from bone marrow.