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.
CD169+ microvesicles (MVs) from subcapsular sinus macrophages (SSMs) mediate cellular crosstalk between SSMs and light zone follicular dendritic cells (LZ FDCs). The MVs are closely associated with immune complexes (ICs), which suggests the role of MVs in antigen transfer and modulation of FDC maturation.
滤泡树突状细胞(FDCs)是一种特殊类型的基质细胞,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)极化为亮区(LZ)和暗区(DZ)。尽管FDC在支持体液免疫应答中起着不可或缺的作用,但其调节需求仍未完全明确。在这项研究中,我们意外地观察到B细胞区有来自被膜下窦巨噬细胞(SSM)的CD169⁺微泡(MVs)聚集,这些微泡与FDC网络紧密相关。有趣的是,在次级滤泡的生发中心亮区FDC以及初级滤泡中预先确定的亮区FDC上都检测到CD169⁺微泡的选择性沉积。由于SSM缺失导致的CD169⁺微泡的消除,使得FDC中亮区相关基因的表达显著降低。此外,我们发现CD169⁺微泡能够与荧光标记的含抗原免疫复合物(ICs)共定位,这支持了CD169⁺微泡在将抗原运输到FDC网络中可能发挥的作用。因此,我们的数据揭示了FDC与位于B细胞滤泡外的SSM之间通过SSM释放的微泡存在密切的相互作用,为FDC成熟和极化的调节机制提供了新的视角。
来自被膜下窦巨噬细胞(SSMs)的CD169⁺微泡(MVs)介导了SSMs与亮区滤泡树突状细胞(LZ FDCs)之间的细胞间相互作用。这些微泡与免疫复合物(ICs)密切相关,这表明微泡在抗原转移以及FDC成熟的调节中发挥作用。