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In addition to coordinated actions between various tightly packed immune cells, such as lymphocytes and myeloid cells, stromal cells, as a dense reticular network in LNs, play an essential role in maintaining immune homeostasis and shaping immune responses through intimate crosstalk with neighboring immune cells that helps determine the localization, activation state, and functional outcome of the latter.
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Lymph nodes (LNs) are critical secondary lymphoid tissues that are strategically positioned throughout the body to filter invading pathogens or antigens draining from local tissues. 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. 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. The ablation of CD169 + MVs, resulting from SSM depletion, resulted in significantly decreased expression of LZ-related genes in FDCs. 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. 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.
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Despite the indispensable role of FDCs in supporting humoral responses, the FDC regulatory requirements remain incompletely defined. When inflammation occurs, the FDC network is reorganized to support germinal center (GC) polarization into the light zone (LZ) and dark zone (DZ). Follicular dendritic cells (FDCs) are a specialized type of stromal cells that exclusively reside in B-cell follicles.