The Conduit System Transports Soluble Antigens from the Afferent Lymph to Resident Dendritic Cells in the T Cell Area of the Lymph Node

Abstract

Resident dendritic cells (DC) within the T cell area of the lymph node take up soluble antigens that enter via the afferent lymphatics before antigen carrying DC arrive from the periphery. The reticular network within the lymph node is a conduit system forming the infrastructure for the fast delivery of soluble substances from the afferent lymph to the lumen of high endothelial venules (HEVs). Using high-resolution light microscopy and 3D reconstruction, we show here that these conduits are unique basement membrane-like structures ensheathed by fibroblastic reticular cells with occasional resident DC embedded within this cell layer. Conduit-associated DC are capable of taking up and processing soluble antigens transported within the conduits, whereas immigrated mature DC occur remote from the reticular fibers. The conduit system is, therefore, not a closed compartment that shuttles substances through the lymph node but represents the morphological equivalent to the filtering function of the lymph node.

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

“…Fibroblastic reticular cells (FRC), identified by the marker ERTR7, line the conduit system, which transports small lymph borne antigens inside its extracellular matrix filled core to the abluminal side of HEV [4]. Our present study investigating the diffusion of 10-kDa FITC-dextran confirmed these observations (Fig.…”

“…Large molecules are retained in subcapsular and medullary sinuses, whereas small lymph-borne molecules with a molecular weight below 70 kDa or a diameter smaller than 4 nm can gain access to the cortex of lymph nodes [3]. Their transport is directed by a network of collagen type I -containing reticular fibers ensheathed by a single layer of fibroblastic reticular cells (FRC) [4]. The reticular network connects the subcapsular sinus and HEV by interweaving its collagen fibers with those of the extracellular matrix of both compartments [5].…”

“…The extracellular matrix inside the FRC network has been termed conduit [6] due to its function as transporting system for small soluble antigens from the afferent lymph directly to the HEV, without percolating through the lymphocyte compartment [3]. Besides its critical function in directing the transport of soluble antigens, the FRC network orchestrates the directed movement of dendritic cells (DC), T and B cells within the lymph node to enhance the frequency of their encounters [4,7].…”

The Lymph Node Revisited: Development, Morphology, Functioning, and Role in Triggering Primary Immune Responses

“…Figure 4 of Gretz et al (1997) was presented to support the existence of ''cortical'' sinuses, but none can be seen. Recently, Sixt et al (2005) reported that drained dextrans accumulate in ''paracortical'' sinuses, but none were illustrated and to our knowledge they do not exist. Gretz et al (1997) said ''that the elegant form'' of the paracortical cords ''dictates, in large part, the marvelous efficiency of secondary lymphoid tissues in facilitating and regulating immune responses.''…”

“…They added that activation requiring the encounter of an antigen (or an antigen-presenting cell: APC) and a rare competent circulating naïve lymphocyte-and how that encounter occurs-depend on morphological features of the lymph node's parenchymal components, so that knowledge of lymph node morphology is essential for understanding its immune function. This opinion was shared by Cyster (1999), Crivaletto et al (2004), and Sixt et al (2005) who along with Gretz et al (1996) proposed scenarios for the triggering of a primary response in the lymph node. However, these scenarios may directly transpose in vitro findings to the in vivo condition, while ignoring the organ's complexity.…”