A B cell culture system using BAFF, IL-4 and IL-21 was recently developed that generates B cells with phenotypic and functional characteristics of in vivo-generated germinal center (GC) B cells. Here, we observe discrete influences of each exogenous signal on the expansion and differentiation of a CD40L-activated B cell pool. IL-4 was expressly necessary, but neither BAFF nor IL-21 was required for B cell acquisition of the GC B cell phenotypes of peanut agglutinin binding and loss of CD38 and IgD expression. Both IL-4 and IL-21 enhanced cell cycle entry upon initial activation dose-dependently, and did so additively. Importantly, while both cytokines acted in concert to increase overall BCL6 expression amounts, IL-21 exposure uniquely caused a small proportion of cells to attain a higher level of BCL6 expression, reminiscent of in vivo GC B cells. In contrast, BAFF supported survival of a fraction of memory-like B cells in extended cultures after removal of surrogate T cell-help signals. Thus, by separably programming proliferation, survival and GC phenotype acquisition, IL-4, BAFF and IL-21 drive distinct components of activated B cell fate.

中文翻译：

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BAFF，IL-4和IL-21分别在体外编程控制生发中心样表型，BCL6表达，CD40L活化B细胞的增殖和存活。

最近开发了使用BAFF，IL-4和IL-21的AB细胞培养系统，该系统可产生具有体内生成的生发中心（GC）B细胞的表型和功能特征的B细胞。在这里，我们观察到每个外源信号对CD40L激活的B细胞池的扩增和分化的离散影响。IL-4是明确必需的，但B细胞获取花生凝集素结合的GC B细胞表型以及CD38和IgD表达的丧失都不需要BAFF和IL-21。IL-4和IL-21都在初始激活时剂量依赖性地增强了细胞周期的进入，并且相加地如此。重要的是，尽管两种细胞因子协同作用以增加总体BCL6表达量，但IL-21暴露独特地引起小部分细胞达到更高水平的BCL6表达，令人联想到体内GC B细胞。相反，在去除替代性T细胞帮助信号后，BAFF支持一部分记忆样B细胞在扩展培养物中的存活。因此，通过分别编程增殖，存活和GC表型获得，IL-4，BAFF和IL-21驱动活化的B细胞命运的不同成分。