T follicular helper (Tfh) and regulatory (Tfr) cells are terminally differentiated cells found in germinal centers (GCs), specialized secondary lymphoid organ structures dedicated to antibody production. As such, follicular T (Tfol) cells are supposed to be specific for immunizing antigens, which has been reported for Tfh cells but is debated for Tfr cells. Here, we used high-throughput T cell receptor (TCR) sequencing to analyze the repertoires of Tfh and Tfr cells, at homeostasis and after immunization with self- or foreign antigens. We observed that, whatever the conditions, Tfh and Tfr cell repertoires are less diverse than those of effector T cells and Treg cells of the same tissues; surprisingly, these repertoires still represent thousands of different sequences, even after immunization with a single antigen that induces a 10-fold increase in Tfol cell numbers. Thorough analysis of the sharing and network of TCR sequences revealed that a specific response to the immunizing antigen can only, but hardly, be detected in Tfh cells immunized with a foreign antigen and Tfr cells immunized with a self-antigen. These antigen-specific responses are obscured by a global stimulation of Tfh and Tfr cells that appears to be antigen-independent. Altogether, our results suggest a major bystander Tfol cell activation during the immune response in the GCs.

T滤泡辅助细胞（Tfh）和调节性（Tfr）细胞是在生发中心（GC）中发现的终末分化细胞，生发中心（GCs）是专门用于抗体生产的专门的次级淋巴器官结构。因此，卵泡T（Tfol）细胞被认为对免疫抗原具有特异性，这已被报道用于Tfh细胞，但对于Tfr细胞却存在争议。在这里，我们使用高通量T细胞受体（TCR）测序来分析Tfh和Tfr细胞在体内平衡时以及在用自身或外源抗原免疫后的所有组成。我们观察到，无论条件如何，Tfh和Tfr细胞的组成都比相同组织的效应T细胞和Treg细胞的多样性少。令人惊讶的是，这些曲目仍然代表着数千种不同的序列，即使使用单一抗原免疫后也会诱导Tfol细胞数量增加10倍。对TCR序列共享和网络的透彻分析表明，在用外源抗原免疫的Tfh细胞和用自身抗原免疫的Tfr细胞中，仅能检测到对免疫抗原的特异性反应，而很难检测到。这些抗原特异性反应被似乎不依赖抗原的Tfh和Tfr细胞的整体刺激所掩盖。总之，我们的结果表明，GC免疫应答期间主要的旁观者Tfol细胞活化。这些抗原特异性反应被似乎不依赖抗原的Tfh和Tfr细胞的整体刺激所掩盖。总之，我们的结果表明，GC免疫应答期间主要的旁观者Tfol细胞活化。这些抗原特异性反应被似乎不依赖抗原的Tfh和Tfr细胞的整体刺激所掩盖。总之，我们的结果表明，GC免疫应答期间主要的旁观者Tfol细胞活化。