Abstract
The conduit network is a hallmark of lymph node microanatomy, but lack of suitable imaging technology has prevented comprehensive investigation of its topology. We employed an extended-volume imaging system to capture the conduit network of an entire murine lymph node (comprising over 280,000 segments). The extensive 3D images provide a comprehensive overview of the regions supplied by conduits, including perivascular sleeves and distinctive "follicular reservoirs" within B cell follicles, surrounding follicular dendritic cells. A 3D topology map of conduits within the T-cell zone showed homogeneous branching, but conduit density was significantly higher in the superficial T-cell zone compared with the deep zone, where distances between segments are sufficient for T cells to lose contact with fibroblastic reticular cells. This topological mapping of the conduit anatomy can now aid modeling of its roles in lymph node function, as we demonstrate by simulating T-cell motility in the different T-cell zones.
Highlights
Sophisticated immune responses are organized within the highly structured microanatomy of lymph nodes (LNs) where stromal cell networks support the circulation, maintenance, and interaction of highly motile hematopoietic cell types on their continuous quest for cognate antigen [1,2,3]
Studies of the LN conduit system have relied on microscopic images with limited depth information
The conduit network is most structured in the central T-cell zone (TCZ) (Fig 1D) and is sparse in the B cell follicles, with only a few channels running beside any one follicle (Fig 1E)
Summary
Sophisticated immune responses are organized within the highly structured microanatomy of lymph nodes (LNs) where stromal cell networks support the circulation, maintenance, and interaction of highly motile hematopoietic cell types on their continuous quest for cognate antigen [1,2,3]. A key feature of the LN organization is the mesh-like network of fibroblastic reticular cells (FRCs) spanning the LN paracortex, the main homing zone for T cells [4,5]. FRCs organize LN microenvironments and control T-cell life in many ways by providing survival signals, aiding migration, and restricting T-cell activation [6,7]. They express the chemokines C-C motif chemokine ligand 19 (CCL19) and C-C motif chemokine ligand 21 (CCL21), important cues for motility, compartmentalization, and retention of C-C chemokine receptor type 7 (CCR7)-expressing T cells, B cells, and dendritic cells (DCs) [3,8,9]. FRCs appear to be involved in B cell homeostasis, by providing the B cell survival factor BAFF
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