Phenotypic Modulation of the Stromal Reticular Network in Normal and Neoplastic Lymph Nodes: Tissue Transglutaminase Reveals Coordinate Regulation of Multiple Cell Types

• Published in: The American journal of pathology Vol. 163; no. 1; pp. 165 - 174
• Main Authors: Thomazy, Vilmos A, Vega, Francisco, Medeiros, L. Jeffrey, Davies, Peter J, Jones, Dan
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01-07-2003; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Hematology; Humans; Immunohistochemistry; Interleukin-4 - metabolism; Investigative techniques, diagnostic techniques (general aspects); Lymph Nodes - cytology; Lymph Nodes - enzymology; Lymph Nodes - pathology; Lymphoma - enzymology; Lymphoma - pathology; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phenotype; Regular; Stromal Cells - cytology; Stromal Cells - enzymology; Transcription, Genetic; Transglutaminases - genetics; Transglutaminases - metabolism; Multiple; Lymph node; Enzyme; Transferases; Stroma; Malignant tumor; Aminoacyltransferases; Pathology; Tissue; Phenotype; Adenopathy; Protein-glutamine γ-glutamyltransferase; Cell
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63640-1

The lymph node paracortex is composed of a network of fibroblastic reticular cells (FRC) and reticular fibers linking sinuses to blood vessels. Using immunostaining for the inducible enzyme/adhesion molecule tissue transglutaminase (TG), we demonstrate coordinate regulation of multiple stromal cell types of this reticular network including FRC, endothelial cells and sinus lining cells. Tissue transglutaminase is expressed at low levels in the paracortex around primary follicles but is markedly up-regulated in stromal cells around hyperplastic germinal centers and then down-regulated around regressing follicles. In cultured FRC, TG is induced 5- to 20-fold and becomes colocalized with matrix proteins by treatment with interleukin-4, but not by other cytokines that are commonly increased in lymph upon immune activation. Coordinate TG up-regulation is observed surrounding nodules of follicular lymphoma (14 of 15 cases) and in the FRC and endothelium of classical Hodgkin's disease, two tumor types that also showed an activated paracortical phenotype. Small lymphocytic lymphoma showed minimal TG staining, with other lymphoma types showing patterns suggesting differential TG regulation. Using TG as a stromal marker, we have identified differential modulation of the phenotype of the lymph node reticular network that parallels change in the B-cell compartment.