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CD169 滤泡树突细胞下窦巨噬细胞衍生的微小囊泡与亮区滤泡树突细胞有关。

CD169 subcapsular sinus macrophage-derived microvesicles are associated with light zone follicular dendritic cells.

机构信息

Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Eur J Immunol. 2022 Oct;52(10):1581-1594. doi: 10.1002/eji.202249879. Epub 2022 Aug 10.

Abstract

Follicular dendritic cells (FDCs) are a specialized type of stromal cells that exclusively reside in B-cell follicles. When inflammation occurs, the FDC network is reorganized to support germinal center (GC) polarization into the light zone (LZ) and dark zone (DZ). Despite the indispensable role of FDCs in supporting humoral responses, the FDC regulatory requirements remain incompletely defined. In this study, we unexpectedly observed an accumulation of CD169 subcapsular sinus macrophage (SSM)-derived microvesicles (MVs) in the B-cell zone, which were tightly associated with the FDC network. Interestingly, a selective deposition of CD169 MVs was detected in both GC LZ FDCs in secondary follicles and on predetermined LZ FDCs in primary follicles. The ablation of CD169 MVs, resulting from SSM depletion, resulted in significantly decreased expression of LZ-related genes in FDCs. In addition, we found that CD169 MVs could colocalize with fluorescently tagged antigen-containing immune complexes (ICs), supporting a possible role of CD169 MVs in transporting antigens to the FDC network. Thus, our data reveal intimate crosstalk between FDCs and SSMs located outside B-cell follicles via SSM-released MVs, providing a novel perspective on the mechanisms underlying the regulation of FDC maturation and polarization.

摘要

滤泡树突状细胞(FDC)是一种专门的基质细胞,仅存在于 B 细胞滤泡中。当发生炎症时,FDC 网络会重新组织,以支持生发中心(GC)向亮区(LZ)和暗区(DZ)的极化。尽管 FDC 在支持体液反应方面具有不可或缺的作用,但 FDC 的调节要求仍不完全明确。在这项研究中,我们意外地观察到在 B 细胞区积聚了源自滤泡被膜下窦巨噬细胞(SSM)的 CD169 衍生的微囊泡(MVs),这些微囊泡与 FDC 网络紧密相关。有趣的是,在次级滤泡的 GC LZ FDC 和初级滤泡中预先确定的 LZ FDC 上都检测到 CD169 MVs 的选择性沉积。由于 SSM 耗竭导致 CD169 MVs 的清除,导致 FDC 中与 LZ 相关的基因表达显著下降。此外,我们发现 CD169 MVs 可以与荧光标记的含有抗原的免疫复合物(ICs)共定位,这支持 CD169 MVs 在将抗原转运到 FDC 网络中的可能作用。因此,我们的数据揭示了 FDC 和位于 B 细胞滤泡外的 SSM 之间通过 SSM 释放的 MV 进行的密切串扰,为 FDC 成熟和极化的调节机制提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aeb/9804338/550e4e91457e/EJI-52-1581-g003.jpg

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