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Abstract
The spatiotemporal regulation of immune responses in the lymph node (LN) depends on its sophisticated tissue architecture, consisting of several subcompartments supported by distinct fibroblastic stromal cells (FSCs). However, the intricate details of stromal structures and associated FSC subsets are not fully understood. Using several gene reporter mice, we sought to discover unrecognized stromal structures and FSCs in the LN. The four previously identified FSC subsets in the cortex are clearly distinguished by the expression pattern of reporters including PDGFRβ, CCL21-ser, and CXCL12. Herein, we identified a unique FSC subset expressing both CCL21-ser and CXCL12 in the deep cortex periphery (DCP) that is characterized by preferential B cell localization. This subset was clearly different from CXCL12highLepRhigh FSCs in the medullary cord, which harbors plasma cells. B cell localization in the DCP was controlled chiefly by CCL21-ser and, to a lesser extent, CXCL12. Moreover, the optimal development of the DCP as well as medulla requires B cells. Together, our findings suggest the presence of a unique microenvironment in the cortex-medulla boundary and offer an advanced view of the multi-layered stromal framework constructed by distinct FSC subsets in the LN.
Highlights
Lymph nodes (LNs) are key sites for the induction of adoptive immunity, and this occurs through the filtering of lymph fluid that is drained form peripheral tissues and the monitoring of antigenic information
fibroblastic stromal cells (FSCs) in the medullary cord (MC) showed high fluorescent protein (FP) expression in Cxcl12-EGFP mice and harbored clusters of plasma cells within the network, whereas plasma cells were rarely observed in the deep cortex periphery (DCP) (Figure 8E). Quantitative analysis supported this preferential plasma cell localization in the MC but not in the DCP (Figures 8F,G), whereas a substantial fraction of B cells was localized to the MC (Figures 3, 4). These results suggest that the microenvironment of the MC is distinguishable from the DCP, which is composed of a different FSC subset
This study revealed that a unique FSC subset constitutes the framework of a subcompertment in the deep cortex, which was previously poorly understood
Summary
Lymph nodes (LNs) are key sites for the induction of adoptive immunity, and this occurs through the filtering of lymph fluid that is drained form peripheral tissues and the monitoring of antigenic information. Lymph Node Stromal Cell Subsets localized to form functionally distinct areas [1, 2]. Such tissue arrangement is probably optimized for the spatiotemporal regulation of immune responses, the fundamental principles associated with the establishment of this architecture remain largely unclear. A structural unit composed of one paracortex and several follicles is termed a “compartment” [3] or “lobule” [4, 5], and a single mouse LN has one or more compartments [6]. Substructures such as the follicle or the paracortex within a compartment should be classified as “subcompartments.”
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