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随后的Myc表达量成正比。然而，由于Myc mRNA 及其相应蛋白的寿命非常短，目前尚不清楚 T 细胞如何在阳性选择的 B 细胞中诱导持续的Myc水平。在这里，通过原位直接可视化 mRNA 和活性转录位点，我们发现转录爆发的增加在 GC 中 B 细胞正选择期间促进Myc表达。升高的 T 细胞帮助信号主要提高 GC 中表达Myc的细胞百分比，而不是增加每个细胞的Myc转录本数量。原位转录起始位点的可视化显示，T 细胞有助于促进主要位于 LZ 顶端边缘的 GC B 细胞中Myc基因座转录爆发频率的增加。因此， Myc的升高（控制 GC 中 B 细胞的正选择）反映了转录活性随时间的整合，而不是转录物在特定时间点的积累。