T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate
T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate
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DOI：
10.1016/j.immuni.2018.03.027
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发表时间：
2018-04-17
期刊：
影响因子：
32.4
通讯作者：
Kurosaki, Tomohiro
中科院分区：
文献类型：
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作者：
Ise, Wataru;Fujii, Kentaro;Kurosaki, Tomohiro
高亲和力或低亲和力的生发中心(GC)B细胞分别被导向浆细胞或GC循环；然而，对浆细胞命运的承诺如何发生尚不清楚。我们发现，一群光区(LZ)GC细胞，表达转录因子IRF4的Bcl6(Lo)CD69(Hi)和亲和力较高的B细胞受体(BCRs)或亲和力较低的Bcl6(Hi)CD69(Hi)分别有利于浆细胞或循环GC细胞的命运。从机制上讲，CD40对Bcl6(Lo)CD69(Hi)细胞的形成具有剂量依赖性调节作用。此外，我们还发现Bcl6(Lo)CD69(Hi)细胞的细胞间黏附分子-1(ICAM-1)和信号转导淋巴细胞激活分子(SLAM)的表达高于Bcl6(Hi)CD69(Hi)细胞，从而提供了更稳定的T滤泡辅助(Tfh)-GC B细胞接触。这些数据支持一种模型，即对浆细胞的承诺始于GC，并表明TFH-GC B细胞接触的稳定性是易于浆细胞的GC细胞形成的关键。
Higher- or lower-affinity germinal center (GC) B cells are directed either to plasma cell or GC recycling, respectively; however, how commitment to the plasma cell fate takes place is unclear. We found that a population of light zone (LZ) GC cells, Bcl6(lo)CD69(hi) expressing a transcription factor IRF4 and higher-affinity B cell receptors (BCRs) or Bcl6(hi)CD69(hi) with lower-affinity BCRs, favored the plasma cell or recycling GC cell fate, respectively. Mechanistically, CD40 acted as a dose-dependent regulator for Bcl6(lo)CD69(hi) cell formation. Furthermore, we found that expression of intercellular adhesion molecule 1 (ICAM-1) and signaling lymphocytic activation molecule (SLAM) in Bcl6(lo)CD69(hi) cells was higher than in Bcl6(hi)CD69(hi) cells, thereby affording more stable T follicular helper (Tfh)-GC B cell contacts. These data support a model whereby commitment to the plasma cell begins in the GC and suggest that stability of Tfh-GC B cell contacts is key for plasma cell-prone GC cell formation.