B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity.
B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity.
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DOI：
10.1126/science.1213368
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发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Shlomchik MJ
中科院分区：
文献类型：
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作者：
Khalil AM;Cambier JC;Shlomchik MJ
老年中心（GC）产生记忆B和浆细胞，这对长期体液免疫至关重要。选择性扩增具有高亲和力B细胞受体（BCR）的GC B细胞。为了实现这种选择，这些细胞的BCR被认为与具有较低亲和力的细胞不同。我们发现，令人惊讶的是，大多数增殖的GC B细胞没有表现出活跃的BCR信号。相反，自发和诱导的信号传导受到磷酸酶活性增加的限制。因此，SHP-1和SHIP-1在GC细胞中过度磷酸化，并在连接后与BCR保持共定位。此外，还需要SHP-1进行GC维护。有趣的是，处于细胞周期G2期的GC B细胞恢复了对BCR刺激的反应性。这些数据对如何在GC中选择更高亲和力的B细胞具有影响。
Germinal centers (GCs) generate memory B and plasma cells, essential for long-lived humoral immunity. GC B cells with high affinity B cell receptors (BCRs) are selectively expanded. To enable this selection, BCRs of such cells are thought to signal differently from those with lower affinity. We show that, surprisingly, most proliferating GC B cells did not demonstrate active BCR signaling. Rather, spontaneous and induced signaling was limited by increased phosphatase activity. Accordingly, both SHP-1 and SHIP-1 were hyperphosphorylated in GC cells and remained colocalized with BCRs after ligation. Furthermore, SHP-1 was required for GC maintenance. Intriguingly, GC B cells in the cell cycle G2 period regained responsiveness to BCR stimulation. These data have implications for how higher affinity B cells are selected in the GC.