Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs). At these sites, B cells mutate their antibody-encoding genes in the dark zone, followed by preferential selection of the high-affinity variants in the light zone by T cells. The strength of the T cell–derived selection signals is proportional to the B cell receptor affinity and to the magnitude of subsequent Myc expression. However, because the lifetime of Myc mRNA and its corresponding protein is very short, it remains unclear how T cells induce sustained Myc levels in positively selected B cells. Here, by direct visualization of mRNA and active transcription sites in situ, we found that an increase in transcriptional bursts promotes Myc expression during B cell positive selection in GCs. Elevated T cell help signals predominantly enhance the percentage of cells expressing Myc in GCs as opposed to augmenting the quantity of Myc transcripts per individual cell. Visualization of transcription start sites in situ revealed that T cell help promotes an increase in the frequency of transcriptional bursts at the Myc locus in GC B cells located primarily in the LZ apical rim. Thus, the rise in Myc , which governs positive selection of B cells in GCs, reflects an integration of transcriptional activity over time rather than an accumulation of transcripts at a specific time point.

中文翻译：

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T 细胞在正选择过程中帮助诱导生发中心 B 细胞中 Myc 转录爆发

抗体亲和力成熟发生在生发中心 (GC) 内的次级淋巴器官中。在这些位点，B 细胞在暗区突变其抗体编码基因，然后 T 细胞优先选择明区的高亲和力变体。 T 细胞衍生的选择信号的强度与 B 细胞受体亲和力以及后续选择信号的强度成正比。我的C表达。然而，由于生命周期我的CmRNA及其相应的蛋白质非常短，目前尚不清楚T细胞如何诱导持续的我的C阳性选择的 B 细胞中的水平。在这里，通过直接观察 mRNA 和原位活性转录位点，我们发现转录爆发的增加促进了我的CGC 中 B 细胞正选择期间的表达。升高的 T 细胞帮助信号主要增强细胞表达的百分比我的C在 GC 中，而不是增加我的C每个细胞的转录本。原位转录起始位点的可视化表明，T 细胞有助于促进转录起始位点的转录爆发频率增加。我的CGC B 细胞中的位点主要位于 LZ 顶端边缘。因此，上升我的C控制 GC 中 B 细胞的正选择，反映了转录活性随时间的整合，而不是特定时间点转录物的积累。