Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses
Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses
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DOI：
10.1016/j.bpj.2023.10.010
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发表时间：
2024-08-06
影响因子：
3.4
通讯作者：
Spillane，Katelyn M.
中科院分区：
文献类型：
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作者：
Iliopoulou，Maro;Bajur，Anna T.;Spillane，Katelyn M.
被膜下窦巨噬细胞(SSM)通过形成免疫屏障来控制抗原从淋巴到淋巴滤泡的运输，从而在免疫防御中发挥关键作用。SSMS通过将抗原直接提供给幼稚的B细胞和向滤泡树突状细胞提供抗原来传播生发中心反应来参与抗体反应。尽管SSM在免疫反应中发挥着突出的作用，但人们对它们的细胞生物学知之甚少，因为它们在技术上很难在体外分离和研究。在这里，我们使用多色荧光显微镜来鉴定培养中的淋巴结来源的SSM。我们重点研究了SSM作为抗原提呈细胞的作用，发现它们的肌动蛋白细胞骨架调节细胞表面展示的多价抗原(免疫复合体[ICs])的空间组织和移动。此外，我们确定SSMS是机械敏感细胞，通过改变肌动蛋白细胞骨架的结构来响应细胞外基质刚性的变化，从而导致细胞形态、膜形貌和IC迁移率的变化。当SSMS和B细胞形成免疫突触时，细胞外基质刚性的变化也会调节肌动蛋白的重塑。这改变了B细胞的突触持续时间，但不改变IC内化或NF-κB的激活。综上所述，我们的数据表明，机械微环境可能通过调节SSMS的抗原提呈的物理特征来影响B细胞的反应。
Subcapsular sinus macrophages (SSMs) play a key role in immune defense by forming immunological barriers that control the transport of antigens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal center reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro. Here, we used multicolor fluorescence microscopy to identify lymph node-derived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells, and found that their actin cytoskeleton regulates the spatial organization and mobility of multivalent antigens (immune complexes [ICs]) displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and IC mobility. Changes to extracellular matrix rigidity also modulate actin remodeling by both SSMs and B cells when they form an immune synapse. This alters synapse duration but not IC internalization nor NF-κB activation in the B cell. Taken together, our data reveal that the mechanical microenvironment may influence B cell responses by modulating physical characteristics of antigen presentation by SSMs.