Lymphotoxin-beta receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes.
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.
Huber
Christoph
C
Institute of Neuropathology, University Hospital of Zürich, Zürich, Switzerland.
Thielen
Caroline
C
Seeger
Harald
H
Schwarz
Petra
P
Montrasio
Fabio
F
Wilson
Mark R
MR
Heinen
Ernst
E
Fu
Yang-Xin
YX
Miele
Gino
G
Aguzzi
Adriano
A
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D051152:Clusterin; D020566:Dendritic Cells, Follicular / Q000737:chemistry / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000737:chemistry / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D053259:Lymphotoxin beta Receptor; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D012995:Solubility; D014158:Transcription, Genetic
D019138:Antibodies, Blocking; C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018832:Molecular Chaperones; D018124:Receptors, Tumor Necrosis Factor