Cutting Edge: An In Vivo Reporter Reveals Active B Cell Receptor Signaling in the Germinal Center
Cutting Edge: An In Vivo Reporter Reveals Active B Cell Receptor Signaling in the Germinal Center
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DOI：
10.4049/jimmunol.1403086
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发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Zikherman, Julie
中科院分区：
文献类型：
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作者：
Mueller, James;Matloubian, Mehrdad;Zikherman, Julie
持久的抗体反应依赖于生发中心(GC)，在那里，从随机突变的池中挑选携带高亲和力Ag受体的B细胞，以填充记忆和浆细胞隔间。BCR下游的信号在GC B细胞中受到抑制，这增加了推动这些关键选择事件的可能性，即抗原提呈和对T细胞的竞争帮助，而不是本身依赖于银的信号本身。在这项研究中，我们使用BCR信号的体内报告基因Nur77-EGFP来证明，尽管BCR信号在GC B细胞中减少，但一小部分具有GC光区表型(抗原和滤泡辅助T细胞相遇的位置)的细胞表达更高水平的GFP。我们发现这些细胞表现出体细胞的高突变、信号和选择的基因表达特征，并在体内接受BCR信号。
Long-lasting Ab responses rely on the germinal center (GC), where B cells bearing high-affinity Ag receptors are selected from a randomly mutated pool to populate the memory and plasma cell compartments. Signaling downstream of the BCR is dampened in GC B cells, raising the possibility that Ag presentation and competition for T cell help, rather than Ag-dependent signaling per se, drive these critical selection events. In this study we use an in vivo reporter of BCR signaling, Nur77-eGFP, to demonstrate that although BCR signaling is reduced among GC B cells, a small population of cells exhibiting GC light zone phenotype (site of Ag and follicular helper T cell encounter) express much higher levels of GFP. We show that these cells exhibit somatic hypermutation, gene expression characteristic of signaling and selection, and undergo BCR signaling in vivo.