Division of Immune Cell Biology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Science. 2013 Jun 28;340(6140):1587-90. doi: 10.1126/science.1237572. Epub 2013 May 16.
The generation of high-affinity antibodies depends on the ability of B cells to extract antigens from the surfaces of antigen-presenting cells. B cells that express high-affinity B cell receptors (BCRs) acquire more antigen and obtain better T cell help. However, the mechanisms by which B cells extract antigen remain unclear. Using fluid and flexible membrane substrates to mimic antigen-presenting cells, we showed that B cells acquire antigen by dynamic myosin IIa-mediated contractions that pull out and invaginate the presenting membranes. The forces generated by myosin IIa contractions ruptured most individual BCR-antigen bonds and promoted internalization of only high-affinity, multivalent BCR microclusters. Thus, B cell contractility contributes to affinity discrimination by mechanically testing the strength of antigen binding.
高亲和力抗体的产生取决于 B 细胞从抗原呈递细胞表面提取抗原的能力。表达高亲和力 B 细胞受体 (BCR) 的 B 细胞能获取更多的抗原并获得更好的 T 细胞辅助。然而，B 细胞提取抗原的机制仍不清楚。本研究使用具有流动性和灵活性的膜基质来模拟抗原呈递细胞，结果表明，B 细胞通过肌球蛋白 IIa 介导的收缩来获取抗原，这种收缩会将呈递膜拉出并内陷。肌球蛋白 IIa 收缩产生的力会破坏大多数单个 BCR-抗原结合，并促进只有高亲和力、多价的 BCR 微簇内化。因此，B 细胞的收缩能力通过机械测试抗原结合的强度来促进亲和力的区分。
