T cell help is a crucial component of the normal humoral immune response, yet whether it promotes or restrains autoreactive B cell responses remains unclear. Here, we observe that autoreactive germinal centers require T cell help for their formation and persistence. Using retrogenic chimeras transduced with candidate TCRs, we demonstrate that a follicular T cell repertoire restricted to a single autoreactive TCR, but not a foreign antigen–specific TCR, is sufficient to initiate autoreactive germinal centers. Follicular T cell specificity influences the breadth of epitope spreading by regulating wild-type B cell entry into autoreactive germinal centers. These results demonstrate that TCR-dependent T cell help can promote loss of B cell tolerance and that epitope spreading is determined by TCR specificity.

中文翻译：

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T 细胞帮助塑造 B 细胞耐受性

T 细胞帮助是正常体液免疫反应的重要组成部分，但它是否促进或抑制自身反应性 B 细胞反应仍不清楚。在这里，我们观察到自身反应性生发中心的形成和持续需要 T 细胞的帮助。使用用候选 TCR 转导的逆转录嵌合体，我们证明滤泡 T 细胞库仅限于单个自身反应性 TCR，而不是外来抗原特异性 TCR，足以启动自身反应性生发中心。滤泡 T 细胞特异性通过调节野生型 B 细胞进入自身反应性生发中心来影响表位扩散的广度。这些结果表明，TCR 依赖性 T 细胞有助于促进 B 细胞耐受性的丧失，并且表位扩散是由 TCR 特异性决定的。