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 Ha 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.
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机译: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 细胞获得更多的抗原并获得更好的 T 细胞帮助。然而,B细胞提取抗原的机制尚不清楚。使用流体和柔性膜底物来模拟抗原呈递细胞,我们发现 B 细胞通过动态肌球蛋白 IIa 介导的收缩获得抗原,这些收缩拉出并内陷呈递膜。肌球蛋白 Ha 收缩产生的力破坏了大多数单个 BCR-抗原键,并仅促进了高亲和力、多价 BCR 微团簇的内化。因此,B 细胞收缩力通过机械测试抗原结合强度有助于亲和力鉴别。
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