Lymphotoxin-beta receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes

• Published in: The Journal of immunology (1950) Vol. 174; no. 9; pp. 5526 - 5536
• Main Authors: Huber, Christoph, Thielen, Caroline, Seeger, Harald, Schwarz, Petra, Montrasio, Fabio, Wilson, Mark R, Heinen, Ernst, Fu, Yang-Xin, Miele, Gino, Aguzzi, Adriano
• Format: Journal Article Web Resource
• Language: English
• Published: United States Amer Assoc Immunologists 01.05.2005
• Subjects: Animals; Antibodies, Blocking - administration & dosage; Cell Aggregation - genetics; Cell Aggregation - immunology; Cell Survival - genetics; Cell Survival - immunology; Cells, Cultured; Clusterin; Dendritic Cells, Follicular - chemistry; Dendritic Cells, Follicular - cytology; Dendritic Cells, Follicular - immunology; Dendritic Cells, Follicular - metabolism; Female; Gene Expression Profiling - methods; Gene Expression Regulation - immunology; Germinal Center - immunology; Germinal Center - metabolism; Glycoproteins - genetics; Glycoproteins - physiology; Human health sciences; Immunohistochemistry; Immunologie & maladie infectieuse; Immunology & infectious disease; Lymph Nodes - chemistry; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymph Nodes - metabolism; Lymphotoxin beta Receptor; Mesentery; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Chaperones - genetics; Molecular Chaperones - physiology; Nucleic Acid Hybridization - methods; Oligonucleotide Array Sequence Analysis - methods; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - physiology; Sciences de la santé humaine; Solubility; Transcription, Genetic
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.174.9.5526

Affinity maturation and Ab class switches occur in lymphoid germinal centers (GCs), in which differentiation and maintenance depend on lymphotoxin (LT) signaling and include differentiation of follicular dendritic cells (FDCs). The events leading to FDC and GC maturation are poorly defined. Using several approaches of functional genomics, we enumerated transcripts affected in mice by suppressing LT beta receptor (LTbetaR) signaling and/or overrepresented in FDC-enriched GC isolates. Protein expression analysis of 3 of 12 genes both enriched in FDCs and down-regulated by LTbetaR signaling suppression validated them as FDC markers. Functional analysis of one of these three, clusterin, suggests a role as an FDC-derived trophic factor for GC B cells. Hence, the set of genes presented in this study includes markers emanating from LTbetaR signaling and transcripts relevant to GC and FDC function.