Within lymph nodes (LNs), T follicular helper (T_FH) cells help B cells to produce antibodies, which can either be protective or autoreactive. Here, we demonstrate that murine LN stromal cells (LNSCs) suppress the formation of autoreactive T_FH cells in an antigen-specific manner, thereby significantly reducing germinal center B cell responses directed against the same self-antigen. Mechanistically, LNSCs express and present self-antigens in major histocompatibility complex (MHC) class II, leading to the conversion of naive CD4⁺ T cells into T regulatory (T_REG) cells in an interleukin-2 (IL-2)-dependent manner. Upon blockade of T_REG cells, using neutralizing IL-2 antibodies, autoreactive T_FH cells are allowed to develop. We conclude that the continuous presentation of self-antigens by LNSCs is critical to generate antigen-specific T_REG cells, thereby repressing the formation of T_FH cells and germinal center B cell responses. Our findings uncover the ability of LNSCs to suppress the early activation of autoreactive immune cells and maintain peripheral tolerance.

在淋巴结（LN）中，T卵泡辅助细胞（T _FH）帮助B细胞产生抗体，该抗体可以是保护性的或自身反应性的。在这里，我们证明了鼠LN基质细胞（LNSCs）以抗原特异性的方式抑制了自身反应性T _FH细胞的形成，从而显着减少了针对相同自身抗原的生发中心B细胞反应。从机制上讲，LNSC在主要组织相容性复合物（MHC）II类中表达并呈递自身抗原，从而导致白细胞CD4 ⁺ T细胞以白介素2（IL-2）依赖性方式转化为T调节（T _REG）细胞。 。使用中和性IL-2抗体阻断T _REG细胞后，自身反应性T _FH细胞被允许发育。我们得出结论，LNSCs不断呈递自身抗原对于产生抗原特异性T _REG细胞至关重要，从而抑制T _FH细胞的形成和生发中心B细胞的反应。我们的发现揭示了LNSC抑制自身反应性免疫细胞的早期活化并维持外周耐受的能力。