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* Center for Genomic Medicine, Graduate School of Medicine and
Graduate School of Biostudies, Kyoto University and
Translational Research Center, Kyoto University Hospital, Kyoto, Japan;
Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan;
¶ Laboratory of Immune Cell Regulation, National Institute of Biomedical Innovation, Ibaraki; and
|| Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Moriguchi, Japan
Mesenchymal stromal cells are crucial components of secondary lymphoid organs (SLOs). Organogenesis of SLOs involves specialized stromal cells, designated lymphoid tissue organizer (LTo) in the embryonic anlagen; in the adult, several distinct stromal lineages construct elaborate tissue architecture and regulate lymphocyte compartmentalization. The relationship between the LTo and adult stromal cells, however, remains unclear, as does the precise number of stromal cell types that constitute mature SLOs are unclear. From mouse lymph nodes, we established a VCAM-1+ICAM-1+MAdCAM-1+ reticular cell line that can produce CXCL13 upon LTβR stimulation and support primary B cell adhesion and migration in vitro. A similar stromal population sharing many characteristics with the LTo, designated marginal reticular cells (MRCs), was found in the outer follicular region immediately underneath the subcapsular sinus of lymph nodes. Moreover, MRCs were commonly observed at particular sites in various SLOs even in Rag2–/– mice, but were not found in ectopic lymphoid tissues, suggesting that MRCs are a developmentally determined element. These findings lead to a comprehensive view of the stromal composition and architecture of SLOs.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Grants-In-Aid for Science Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
2 Address correspondence and reprint requests to Dr. Tomoya Katakai, Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Moriguchi 570-8506, Japan. E-mail address: katakait{at}takii.kmu.ac.jp
3 Abbreviations used in this paper: SLO, secondary lymphoid organ; CP, cryptopatch; ECM, extracellular matrix; FAE, follicle-associated epithelium; DC, dendritic cell; FDC, follicular DC; FRC, fibroblastic reticular cell; LT, lymphotoxin; LTi/o, lymphoid tissue inducer/organizer; MRC, marginal reticular cell; NALT, nasal-associated lymphoid tissue; PP, Peyer’s patch; SCS, subcapsular sinus; LN, lymph node; NIK, NF-
B-inducing kinase; ILF, isolated lymphoid follicle; TRANCE, TNF-related activation-induced cytokine; DAPI, 4,6-diamidino-2-phenylindole; PTx, pertussis toxin; MAdCAM-1, mucosal addressin cell adhesion molecule 1; FAE, follicle-associated epithelium.
4 The online version of this article contains supplemental material.
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