Research Unit for Immunodynamics, RIKEN, Research Center for Allergy and Immunology, Yokohama, 230-0045, Japan.
Immunity. 2011 Jun 24;34(6):961-72. doi: 10.1016/j.immuni.2011.03.025.
The transcription factor Bcl6 is essential for the development of germinal center (GC) B cells and follicular helper T (Tfh) cells. However, little is known about in vivo dynamics of Bcl6 protein expression during and after development of these cells. By using a Bcl6 reporter mouse strain, we found that antigen-engaged B cells upregulated Bcl6 before clustering in GCs. Two-photon microscopic analysis indicated that Bcl6 upregulation in pre-GC B cells contributed to sustaining their interactions with helper T cells and was required for their entry to GC clusters. Our data also suggested that Tfh cells gradually downmodulated Bcl6 protein over weeks after development. The Bcl6-low Tfh cells rapidly terminated proliferation and upregulated IL-7 receptor. These results clarify the role of Bcl6 in pre-GC B cell dynamics and highlight the modulation of Bcl6 expression in Tfh cells that persist in the late phase of the antibody response.
转录因子 Bcl6 对于生发中心 (GC) B 细胞和滤泡辅助 T (Tfh) 细胞的发育至关重要。然而，对于这些细胞在发育过程中和发育后 Bcl6 蛋白表达的体内动态变化知之甚少。通过使用 Bcl6 报告小鼠品系，我们发现抗原结合的 B 细胞在 GC 中聚集之前上调了 Bcl6。双光子显微镜分析表明，前 GC B 细胞中 Bcl6 的上调有助于维持它们与辅助 T 细胞的相互作用，并且是它们进入 GC 簇所必需的。我们的数据还表明，Tfh 细胞在发育后数周内逐渐下调 Bcl6 蛋白。Bcl6 低表达的 Tfh 细胞迅速终止增殖并上调 IL-7 受体。这些结果阐明了 Bcl6 在前 GC B 细胞动力学中的作用，并强调了在抗体反应后期持续存在的 Tfh 细胞中 Bcl6 表达的调节。
