B cell antigen extraction is regulated by physical properties of antigen-presenting cells.
B cell antigen extraction is regulated by physical properties of antigen-presenting cells.
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DOI：
10.1083/jcb.201607064
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发表时间：
2017-01-02
期刊：
影响因子：
--
通讯作者：
Tolar P
中科院分区：
文献类型：
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作者：
Spillane KM;Tolar P
为了产生抗体反应，B细胞需要从抗原呈递细胞（APC）中提取抗原。使用新的DNA纳米传感器，Spillane和Tolar表明B细胞抗原提取通过机械力发生，并受APC的物理特性调节。抗体产生和亲和力成熟由B细胞提取和来自免疫突触的抗原内化驱动。然而，提取机制仍然知之甚少。在这里，我们开发基于DNA的纳米传感器来询问两个先前提出的机制，酶释放和机械力。使用人工基质或活细胞呈递的抗原，我们表明B细胞主要使用力依赖性提取，只有在机械力无法检索抗原时才诉诸酶促释放。机械力的使用使得抗原提取对呈递细胞的物理性质敏感。我们发现，滤泡树突状细胞是僵硬的细胞，促进强大的B细胞拉力和严格的亲和力歧视。相比之下，树突状细胞是柔软的，并通过低力促进低亲和力抗原的获得。因此，B细胞突触的机械特性调节抗原提取，表明呈递细胞的不同特性支持B细胞应答的不同阶段。
To mount antibody responses, B cells need to extract antigens from antigen-presenting cells (APCs). Using new DNA nanosensors, Spillane and Tolar show that B cell antigen extraction occurs via mechanical forces and is regulated by physical properties of the APCs. Antibody production and affinity maturation are driven by B cell extraction and internalization of antigen from immune synapses. However, the extraction mechanism remains poorly understood. Here we develop DNA-based nanosensors to interrogate two previously proposed mechanisms, enzymatic liberation and mechanical force. Using antigens presented by either artificial substrates or live cells, we show that B cells primarily use force-dependent extraction and resort to enzymatic liberation only if mechanical forces fail to retrieve antigen. The use of mechanical forces renders antigen extraction sensitive to the physical properties of the presenting cells. We show that follicular dendritic cells are stiff cells that promote strong B cell pulling forces and stringent affinity discrimination. In contrast, dendritic cells are soft and promote acquisition of low-affinity antigens through low forces. Thus, the mechanical properties of B cell synapses regulate antigen extraction, suggesting that distinct properties of presenting cells support different stages of B cell responses.