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Published on: April 9, 2014
CD169+ subcapsular sinus macrophage-derived microvesicles are associated with light zone follicular dendritic cells
Xin Chen1, Yuhan Zheng1, Siming Liu1
1Shanghai 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.
Insights
Subcapsular sinus macrophages (SSMs) release microvesicles (MVs) that regulate follicular dendritic cells (FDCs) and germinal center formation. This study reveals SSM-MVs are crucial for FDC maturation and antigen transport.
Area of Science:
- Immunology
- Cell Biology
Background:
- Follicular dendritic cells (FDCs) are crucial stromal cells in B-cell follicles, organizing germinal center (GC) responses.
- The regulatory mechanisms governing FDC maturation and GC polarization remain incompletely understood.
Purpose of the Study:
- To investigate the role of subcapsular sinus macrophages (SSMs) and their derived microvesicles (MVs) in regulating FDCs.
- To elucidate the contribution of SSM-MVs to germinal center light zone (LZ) organization and function.
Main Methods:
- Observation of CD169+ SSM-derived MVs in B-cell zones and their association with FDCs.
- Selective depletion of SSMs and subsequent analysis of FDC gene expression.
- Colocalization studies of MVs with antigen-containing immune complexes (ICs).
Main Results:
- CD169+ MVs selectively deposit on FDCs in the light zone of germinal centers.
- Depletion of SSMs and their MVs led to reduced expression of LZ-related genes in FDCs.
- SSM-derived MVs were found to colocalize with antigen-containing immune complexes.
Conclusions:
- SSMs and FDCs engage in crosstalk via SSM-released MVs, influencing FDC maturation and GC polarization.
- SSM-derived MVs may play a role in transporting antigens to the FDC network.
- This study provides novel insights into the regulation of FDC function and humoral immunity.
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.
