Fibroblastic Reticular Cell Conduit in Lymph Node Cortex, January 1, 2012

The Fibroblastic Reticular Cell Conduit
The FRCC rapidly conducts soluble materials across lymphatic tissues, including
chemokines and antigens. It also displays ECM & adhesion proteins that support
T- and B-cell migration past dendritic cells to lymphatic tissue compartments. [TR-04-476]

See the Structure of the FRCC which serves as a conduit to transmit signals across the lymph node cortex to dendritic cells and the HEV wall.

This image is from my 1975 paper where the "FRC Conduit" was first described.

See Anderson and Shaw, Sem. Immunol. 5:271-282. for full description of how the FRC Conduit works in the lymph node cortex.

The FRC Conduit is a reticular fiber surrounded by basement membrane and the cytoplasmic process of an FRC. Its 3D structure as a compartment defining network is nicely revealed in the SEM image of LN Reticulum by Ushiki

The FRC Conduit carries both chemokine signals and soluble antigens to mature dendritic cells that are attached along the course of FRCC connecting the subcapsular sinus lining cells with the walls of HEV in the deep cortex. This is regarded as the anatomical basis for the highly orchestrated waves of lymphocyte emigration and antigen presentation that occur in the LN Cortex after soluble antigen enters in from afferent lymph. Later a second wave of antigen presentation follows entry of antigen laden dendritic cells that crawl into the cortex across the floor of the subcapsular lymphatic sinus.

What drives the fluid transudates and soluble materials down the FRCC from the SCS to a High Endothelial Venule and across its wall and into the lumen?

The membranes of lymphatic endothelium lining the subcapsular, intermediate, and cortical sinus networks, along with key blood vascular structures such as the capillaries in the floor of the SCS and the endothelium of HEV deep in the cortex are rich in Aquaporin-1 activity. The presence of aquaporin "pumps" in these structures is intrigueing. Rapid water fluxes across vascular endothelium and across fibroblastic reticular cell membranes might support unidirectional flow of fluids down the FRC Conduit. But, how aquaporins function in lymph nodes will need to be investigated before it can explain FRC Conduit fluid flow.

The FRCC may also be a target of infection by Ebola viruses that can rapidly cross lymphatic tissues or subcutaneous reticular connective tissue via FRC Conduit to enter the blood at postcapillary venules.

References:

Clark, S 1962. The Reticulum of Lymph Nodes in Mice Studied with the Electron Microscope. Am. J. Anat. 110: 217-257. (first electron microscopic study of FRC structure)

Moe, RE. 1964. Electron Microscopic Appearance of the Parenchyma of Lymph Nodes. Am J Anat 114:341-369. (first to speculate that FRC might conduct antigens)

Anderson, AO, and ND Anderson. 1975. Studies on the structure and permeability of the microvasculature in normal rat lymph nodes. Amer. J. Path. 80:387-418. (first evidence that FRC Conduit conducted 40KDa Horse Radish Peroxidase tracer from LN Subcapsular Sinus to HEV wall and lumen within a minute after intralymphatic inoculation)

Anderson, ND, AO Anderson, and RG Wyllie. 1976. Specialized structure and metabolic activities of high endothelial venules in rat lymphatic tissues. Immunology 31:455-473.

Anderson, AO and ND Anderson. 1976. Lymphocyte emigration from high endothelial venules in rat lymph nodes. Immunology 31:731-748.

Chang, TW, E Celis, HN Eisen and F Solomon. 1979. Crawling movements of lymphocytes on and beneath fibroblasts in culture. Proc Natl Acad Sci U S A. 76(6): 2917?2921.

Anderson, AO and ND Anderson. 1981. Structure and Physiology of the Lymphatic System. In: Cellular Functions in Immunity and Inflammation, Chapter 2, pp. 29-72, Oppenheim, JJ, Rosenstreich, DA, and Potter M (eds.), Elsevier-North Holland Publishers, NY. [Author's PDF] (Reticular Cells and Conduit function described on pp58-60.)

Sainte-Marie G, Peng FS. 1986. Diffusion of a lymph-carried antigen in the fiber network of the lymph node of the rat. Cell Tissue Res. 245:481-486. (ex vivo demonstration that fluorescent antigen entered reticular fibers from SCS)

Larsen, CG, AO Anderson, E Appella, JJ Oppenheim, and K Matsushima. 1989. The Neutrophil-Activating Protein (NAP-1) is also chemotactic for T lymphocytes. Science 243:1464-1466. [Author's PDF] (first indication how fast chemokine injected in periphery might change rate of cell traffic at HEV in draining lymph node)

Anderson, AO. 1990. "Structure and organization of the lymphatic system." In Immunophysiology. The role of cells and cytokines in immunity and inflammation. Oppenheim, JJ and E Shevach (eds.), pp. 14-45, Oxford University Press, NY. [Author's PDF]

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