Computational Biology, Discovery Sciences, Janssen Research and Development LLC., 1400 McKean Road, Spring House, PA, United States of America.
PLoS One. 2018 Aug 23;13(8):e0200241. doi: 10.1371/journal.pone.0200241. eCollection 2018.
A model of B cell affinity selection is proposed, and an explanation of peripheral tolerance mechanisms through antibody repertoire editing is presented. We show that affinity discrimination between B cells is driven by a competition between obtaining T cell help and removal of B cells from the light zone, either through apoptosis or by a return to the dark zone of germinal centers. We demonstrate that this mechanism also allows for the negative selection of self reactive B cells and maintenance of B cell tolerance during the Germinal Center reaction. Finally, we demonstrate that clonal expansion upon return to the Germinal Center dark zone amplifies differences in the antigen affinity of B cells that survive the light zone.
提出了 B 细胞亲和力选择的模型，并通过抗体库编辑解释了外周耐受机制。我们表明，B 细胞之间的亲和力差异是由获得 T 细胞帮助和 B 细胞从生发中心的亮区中清除之间的竞争驱动的，这种清除是通过细胞凋亡或返回生发中心的暗区来实现的。我们证明，这种机制还允许自身反应性 B 细胞的阴性选择，并在生发中心反应期间维持 B 细胞耐受。最后，我们证明，返回生发中心暗区后的克隆扩增放大了在亮区存活的 B 细胞的抗原亲和力差异。
