The Journal of Experimental Medicine
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Published 20 September 2004. doi:10.1084/jem.20040254
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 6, 783-795
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Lymph Node Fibroblastic Reticular Cells Construct the Stromal Reticulum via Contact with Lymphocytes

Tomoya Katakai1, Takahiro Hara1, Manabu Sugai1, Hiroyuki Gonda1,2, and Akira Shimizu1,2

1 Center for Molecular Biology and Genetics, Kyoto University
2 Translational Research Center, Kyoto University Hospital, Shogoin-Kawahara-cho, Kyoto 606-8507, Japan

Address correspondence to Tomoya Katakai, Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-4194; Fax: 81-75-751-4190; email: tkatakai{at}virus.kyoto-u.ac.jp

The sophisticated microarchitecture of the lymph node, which is largely supported by a reticular network of fibroblastic reticular cells (FRCs) and extracellular matrix, is essential for immune function. How FRCs form the elaborate network and remodel it in response to lymphocyte activation is not understood. In this work, we established ERTR7+gp38+VCAM-1+ FRC lines and examined the production of the ER-TR7 antigen. Multiple chemokines produced by FRCs induced T cell and dendritic cell chemotaxis and adhesion to the FRC surface. FRCs can secrete the ER-TR7 antigen as an extracellular matrix component to make a reticular meshwork in response to contact with lymphocytes. The formation of the meshwork is induced by stimulation with tumor necrosis factor-{alpha} or lymphotoxin-{alpha} in combination with agonistic antibody to lymphotoxin-ß receptor in a nuclear factor-{kappa}B (RelA)–dependent manner. These findings suggest that signals from lymphocytes induce FRCs to form the network that supports the movement and interactions of immune effectors within the lymph node.

Key Words: lymphoid tissue • stromal cells • reticular network • ER-TR7 • lymphotoxins

Abbreviations used in this paper: BLS, BALB/c LN stroma; ECM, extracellular matrix; FDC, follicular dendritic cell; FRC, fibroblastic reticular cell; GC, germinal center; HEV, high endothelial venule; LT, lymphotoxin; LTi, lymphoid tissue inducer; PTx, pertussis toxin; RF, reticular fiber; RN, reticular network; SCS, subcapsular sinus.


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