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* Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; and
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110
Stromal cells play a crucial role in the organogenesis of lymphoid tissues. We previously identified VCAM-1+ stromal cells in cryptopatches (CP) and isolated lymphoid follicles (ILF) in the small intestine of C57BL/6 mice. Nonhemopoietic stromal cell networks in CP and ILF of adult mice also expressed FDC-M1, CD157 (BP-3), and TNF-related activation-induced cytokine (TRANCE). Individual stromal cells were heterogeneous in their expression of these markers, with not all stromal cells expressing the entire set of stromal cell markers. Expression of VCAM-1, FDC-M1, and CD157 on CP stromal cells was absent in alymphoplasia mice deficient in NF-
B-inducing kinase (NIK) and NIK knockout mice. Administration of lymphotoxin 
receptor (LTR)-Ig to wild-type mice on day 13 resulted in the absence of CP on day 20; delaying administration of LTR-Ig until day 18 resulted in an 80% decrease in the number of CP on day 22 and diminished expression of VCAM-1, FDC-M1, and CD157 on the remaining CP. In sharp contrast, TRANCE expression by stromal cells was completely independent of NIK and LTR. In addition, expression of TRANCE in ILF was concentrated just beneath the follicle-associated epithelium, a pattern of polarization that was also observed in Peyer’s patches. These findings suggest that TRANCE on stromal cells contributes to the differentiation and maintenance of organized lymphoid aggregates in the small intestine.
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1 This work was supported by grants from the National Institutes of Health (DK64730 (to I.R.W.), DK64798 (to R.D.N.), and DK64399 supporting the Imaging Core Facility of the Emory Digestive Diseases Research Development Center).
2 Address correspondence and reprint requests to Dr. Ifor R. Williams, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Whitehead Building 105D, 615 Michael Street, Atlanta, GA 30322. E-mail address: irwilli{at}emory.edu
3 Abbreviations used in this paper: FDC, follicular dendritic cell; LT, lymphotoxin; LTR, LT receptor; CP, cryptopatch; ILF, isolated lymphoid follicle; PP, Peyer’s patch; LTIC, lymphoid tissue inducer cell; BM, bone marrow; TRANCE, TNF-related activation-induced cytokine; RANK, receptor activator of NF-B; FAE, follicle-associated epithelium; NIK, NF-B-inducing kinase; TSA, tyramide signal amplification; PDGFR
, platelet-derived growth factor receptor ; E, embryonic day.
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