论文标题
桥接生发中心B细胞和卵泡树突状细胞的最弱连接限制了抗体亲和力成熟
The weakest link bridging germinal center B cells and follicular dendritic cells limits antibody affinity maturation
论文作者
论文摘要
在体内产生的靶抗原（AGS）产生的抗体（ABS）的亲和力通常远低于最大亲和力。大约25年前，Foote和Eisen解释了“亲和力天花板”如何来自与B细胞可溶性抗原相关的约束。然而，最近的研究表明，生发中心的B细胞（AB亲和成熟发生）并非以可溶性形式获取Ag，而是以卵泡树突状细胞（FDC）的受体结合的免疫复合物（FDC）表示。在这种情况下，亲和力天花板的产生方式尚不清楚。在这里，我们认为天花板源于蛋白质复合物链的最弱环节，该蛋白质复合物链桥接B细胞和FDC，并在AG采集期间被损坏。该假设解释了体内实现的亲和力天花板，并表明加强最弱的联系可以提高天花板并改善AB反应。
The affinity of antibodies (Abs) produced in vivo for their target antigens (Ags) is typically well below the maximum affinity possible. Nearly 25 years ago, Foote and Eisen explained how an 'affinity ceiling' could arise from constraints associated with the acquisition of soluble antigen by B cells. However, recent studies have shown that B cells in germinal centers (where Ab affinity maturation occurs) acquire Ag not in soluble form but presented as receptor-bound immune complexes on follicular dendritic cells (FDCs). How the affinity ceiling arises in such a scenario is unclear. Here, we argue that the ceiling arises from the weakest link of the chain of protein complexes that bridges B cells and FDCs and is broken during Ag acquisition. This hypothesis explains the affinity ceiling realized in vivo and suggests that strengthening the weakest link could raise the ceiling and improve Ab responses.
