The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.
The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.
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DOI：
10.1038/ni.2047
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发表时间：
2011-06-05
影响因子：
30.5
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中科院分区：
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鞘氨醇-1-磷酸受体-2（S1 P2）缺陷小鼠发生弥漫性大B细胞淋巴瘤。然而，S1 P2在正常生发中心（GC）生理中的作用尚不清楚。在这里，我们表明，S1 P2-缺陷型GC B细胞生长超过其野生型对应的慢性建立GC。我们发现，S1 P2-，G12-G13-和p115 RhoGEF介导的Akt的拮抗作用调节细胞活力，并需要在慢性增殖GC的生长控制。我们还发现S1 P2抑制GC B细胞对滤泡化学引诱物的反应，并有助于将细胞限制在GC。此外，S1 P2过表达促进激活的B细胞在卵泡内居中。我们认为，通过抑制Akt的激活和迁移，S1 P2有助于限制GC B细胞的存活和定位到卵泡中心的S1 P低的小生境。
Sphingosine-1-phosphate receptor-2 (S1P2)-deficient mice develop diffuse large B cell lymphoma. However, the role of S1P2 in normal germinal center (GC) physiology is unknown. Here we show that S1P2-deficient GC B cells outgrow their wild-type counterparts in chronically-established GCs. We find that S1P2-, G12–G13- and p115RhoGEF-mediated antagonism of Akt regulates cell viability and is required for growth control in chronically proliferating GCs. We also find that S1P2 inhibits GC B cell responses to follicular chemoattractants and helps confine cells to the GC. Moreover, S1P2 overexpression promotes centering of activated B cells within the follicle. We suggest that by inhibiting Akt activation and migration, S1P2 helps restrict GC B cell survival and localization to an S1P-low niche at the follicle center.