Repression of BCL-6 is required for the formation of human memory B cells in vitro.
Repression of BCL-6 is required for the formation of human memory B cells in vitro.
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DOI：
10.1084/jem.20062104
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发表时间：
2007-04-16
影响因子：
15.3
通讯作者：
Calame, Kathryn
中科院分区：
文献类型：
--
作者：
Kuo, Tracy C;Shaffer, Arthur L;Haddad, Joseph Jr;Choi, Yong Sung;Staudt, Louis M;Calame, Kathryn
记忆B细胞对先前遇到的抗原提供快速保护;然而，这些细胞如何从生殖中心B细胞发育尚不清楚。使用先前描述的使用人扁桃体生发中心B细胞的体外培养系统来研究在人记忆B细胞分化期间发生的转录变化。监测几种已知的晚期B细胞转录因子表达水平的动力学研究表明，BCL-6在体外产生的记忆B细胞中不表达，基因表达谱研究证实BCL-6在这些记忆B细胞中不表达。此外，BCL-6在人B细胞培养物中的异位表达导致形成较少的记忆B细胞。此外，在体外记忆B细胞的表达谱显示了一个独特的模式，包括编码多种共刺激分子和细胞因子受体，抗凋亡蛋白，T细胞趋化因子和转录因子的基因的表达。这些研究建立了定义人类B细胞中记忆B细胞阶段的新的分子标准。
Memory B cells provide rapid protection to previously encountered antigens; however, how these cells develop from germinal center B cells is not well understood. A previously described in vitro culture system using human tonsillar germinal center B cells was used to study the transcriptional changes that occur during differentiation of human memory B cells. Kinetic studies monitoring the expression levels of several known late B cell transcription factors revealed that BCL-6 is not expressed in memory B cells generated in vitro, and gene expression profiling studies confirmed that BCL-6 is not expressed in these memory B cells. Furthermore, ectopic expression of BCL-6 in human B cell cultures resulted in formation of fewer memory B cells. In addition, the expression profile of in vitro memory B cells showed a unique pattern that includes expression of genes encoding multiple costimulatory molecules and cytokine receptors, antiapoptotic proteins, T cell chemokines, and transcription factors. These studies establish new molecular criteria for defining the memory B cell stage in human B cells.