Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter
Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter
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DOI：
10.1016/j.cell.2010.10.032
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发表时间：
2010-11-12
期刊：
影响因子：
64.5
通讯作者：
Nussenzweig, Michel C.
中科院分区：
文献类型：
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作者：
Victora, Gabriel D.;Schwickert, Tanja A.;Nussenzweig, Michel C.
生发中心（GC）反应通过随机突变和选择性克隆扩增具有高亲和力受体的B细胞产生高亲和力抗体。B细胞被选择的机制尚不清楚，就像解剖学上定义的两个GC区域，亮区（LZ）和暗区（DZ）的作用一样。我们将转基因光激活荧光蛋白示踪剂与多光子激光扫描显微镜和流式细胞术相结合，检测解剖定义的LZ和DZ B细胞和GC选择。我们发现B细胞分裂仅限于DZ， B细胞从DZ移动到LZ的净矢量。返回DZ并进行克隆扩增的决定是由GC LZ中的T辅助细胞控制的，它们根据捕获和呈递的抗原数量来区分LZ B细胞。因此，T细胞的帮助，而不是对抗原的直接竞争，是GC选择的限制因素。
The germinal center (GC) reaction produces high-affinity antibodies by random mutation and selective clonal expansion of B cells with high-affinity receptors. The mechanism by which B cells are selected remains unclear, as does the role of the two anatomically defined areas of the GC, light zone (LZ) and dark zone (DZ). We combined a transgenic photoactivatable fluorescent protein tracer with multiphoton laser-scanning microscopy and flow cytometry to examine anatomically defined LZ and DZ B cells and GC selection. We find that B cell division is restricted to the DZ, with a net vector of B cell movement from the DZ to the LZ. The decision to return to the DZ and undergo clonal expansion is controlled by T helper cells in the GC LZ, which discern between LZ B cells based on the amount of antigen captured and presented. Thus, T cell help, and not direct competition for antigen, is the limiting factor in GC selection.