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首页> 外文期刊>Molecular and Cellular Biology >Critical Role of SAP in Progression and Reactivation but Not Maintenance of T Cell-Dependent Humoral Immunity
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Critical Role of SAP in Progression and Reactivation but Not Maintenance of T Cell-Dependent Humoral Immunity

机译：SAP在进展和重新激活而非维持T细胞依赖性体液免疫中的关键作用

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Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter not only for mechanistic reasons but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the lineage commitment factor Bcl-6 in follicular T helper (TFH) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.
机译：信号转导淋巴细胞激活分子（SLAM）相关蛋白（SAP）是在X连锁淋巴组织增生性疾病（一种人类免疫缺陷）中突变的小衔接子分子。 SAP在引发T细胞依赖性B细胞反应（导致生发中心反应，产生高亲和力抗体和B细胞记忆）中起关键作用。但是，尚不知道SAP是否会在这些响应的发起之外发挥作用。解决这一问题的重要性不仅是出于机械原因，还因为考虑到SAP途径的阻断被视为治疗人类自身免疫性疾病的一种手段。使用诱导型SAP缺陷小鼠，我们发现SAP不仅需要启动，而且还需要原代T细胞驱动的B细胞对半抗原的反应进行。在次级免疫应答过程中，重新激活T细胞依赖性B细胞免疫也是必要的。这些活性与SAP在卵泡T辅助细胞（T FH ）中完整表达谱系承诺因子Bcl-6的需求一致。但是，一旦建立了记忆B细胞和长寿的抗体分泌细胞，SAP就可用于维持依赖T细胞的B细胞应答。因此，SAP对于T细胞驱动的B细胞体液免疫的几乎所有阶段都是至关重要的，但对于维护而言却不是。这些发现可能通过靶向SAP途径而对免疫疾病的治疗产生影响。

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