T follicular helper (T_FH) cells are critical in adaptive immune responses to pathogens and vaccines; however, what drives the initiation of their developmental program remains unclear. Studies suggest that a T cell antigen receptor (TCR)-dependent mechanism may be responsible for the earliest T_FH cell–fate decision, but a critical aspect of the TCR has been overlooked: tonic TCR signaling. We hypothesized that tonic signaling influences early T_FH cell development. Here, two murine TCR-transgenic CD4⁺ T cells, LLO56 and LLO118, which recognize the same antigenic peptide presented on major histocompatibility complex molecules but experience disparate strengths of tonic signaling, revealed low tonic signaling promotes T_FH cell differentiation. Polyclonal T cells paralleled these findings, with naive Nur77 expression distinguishing T_FH cell potential. Two mouse lines were also generated to both increase and decrease tonic signaling strength, directly establishing an inverse relationship between tonic signaling strength and T_FH cell development. Our findings elucidate a central role for tonic TCR signaling in early T_FH cell-lineage decisions.

卵泡辅助细胞（T _FH）在对病原体和疫苗的适应性免疫反应中至关重要。然而，什么驱动他们的发展计划的启动尚不清楚。研究表明，T细胞抗原受体（TCR）依赖性机制可能是最早的T _FH细胞命运决定的原因，但是TCR的一个关键方面却被忽略了：补品TCR信号传导。我们假设补品信号传导影响早期T _FH细胞发育。在这里，两个鼠类TCR转基因CD4 ⁺ T细胞LLO56和LLO118能够识别主要组织相容性复合物分子上呈现的相同抗原肽，但具有不同的强直信号强度，显示低强直信号可以促进T _FH细胞分化。多克隆T细胞与这些发现相吻合，其中朴素的Nur77表达可区分T _FH细胞潜力。还产生了两个小鼠品系，以增加和降低滋补信号强度，直接建立了滋补信号强度与T _FH细胞发育之间的反比关系。我们的发现阐明了补体TCR信号在早期T _FH细胞谱系决定中的核心作用。