[en] 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 (LT beta R) 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 LT beta R 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 LT beta R signaling and transcripts relevant to GC and FDC function.
Disciplines :
Immunology & infectious disease
Author, co-author :
Huber, Christoph; University Hospital of Zurich > Insitute of Neuropathology
Thielen, Caroline ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie Humaine
Seeger, Harald; University Hospital of Zurich > Insitute of Neuropathology
Schwarz, Petra; University Hospital of Zurich > Insitute of Neuropathology
Montrasio, Fabio; University Hospital of Zurich > Insitute of Neuropathology
Wilson, Mark
Heinen, Ernst ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine
Fu, Yang-Xin
Miele, Gino; University Hospital of Zurich > Insitute of Neuropathology
Aguzzi, Adriano; University Hospital of Zurich > Insitute of Neuropathology
Language :
English
Title :
Lymphotoxin-beta receptor-dependent genes in lymph node and follicular dendritic cell transcriptomes
Publication date :
01 May 2005
Journal title :
Journal of Immunology
ISSN :
0022-1767
eISSN :
1550-6606
Publisher :
Amer Assoc Immunologists, Bethesda, United States - Maryland
Volume :
174
Issue :
9
Pages :
5526-5536
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
Futterer, A., K. Mink, A. Luz, M. H. Kosco-Vilbois, and K. Pfeffer. 1998. The lymphotoxin β receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 9:59.
Pasparakis, M., L. Alexopoulou, M. Grell, K. Pfizenmaier, H. Bluethmann, and G. Kollias. 1997. Peyer's patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor. Proc. Natl. Acad. Sci. USA 94:6319.
Pfeffer, K., T. Matsuyama, T. M. Kundig, A. Wakeham, K. Kishihara, A. Shahinian, K. Wiegmann, P. S. Ohashi, M. Kronke, and T. W. Mak. 1993. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell 73:457.
Pasparakis, M., L. Alexopoulou, V. Episkopou, and G. Kollias. 1996. Immune and inflammatory responses in TNF α-deficient mice: a critical requirement for TNF α in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response J. Exp. Med. 184:1397.
Korner, H., M. Cook, D. S. Riminton, F. A. Lemckert, R. M. Hoek, B. Ledermann, F. Kontgen, B. Fazekas de St Groth, and J. D. Sedgwick. 1997. Distinct roles for lymphotoxin-α and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue. Eur. J. Immunol. 27:2600.
De Togni, P., J. Goellner, N. H. Ruddle, P. R. Streeter, A. Fick, S. Mariathasan, S. C. Smith, R. Carlson, L. P. Shornick, J. Strauss-Schoenberger, et al. 1994. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703.
Koni, P. A., R. Sacca, P. Lawton, J. L. Browning, N. H. Ruddle, and R. A. Flavell. 1997. Distinct roles in lymphoid organogenesis for lymphotoxins α and β revealed in lymphotoxin β-deficient mice. Immunity 6:491.
Fu, Y. X., H. Molina, M. Matsumoto, G. Huang, J. Min, and D. D. Chaplin. 1997. Lymphotoxin-α (LTα) supports development of splenic follicular structure that is required for IgG responses. J. Exp. Med. 185:2111.
Karrer, U., C. Lopez-Macias, A. Oxenius, B. Odermatt, M. F. Bachmann, U. Kalinke, H. Bluethmann, H. Hengartner, and R. M. Zinkernagel. 2000. Antiviral B cell memory in the absence of mature follicular dendritic cell networks and classical germinal centers in TNFR1-/- mice. J. Immunol. 164:768.
Bouzahzah, F., N. Antoine, L. Simar, and E. Heinen. 1996. Chemotaxis-promoting and adhesion properties of human tonsillar follicular dendritic cell clusters. Res. Immunol. 147:165.
van Eijk, M., and C. de Groot. 1999. Germinal center B cell apoptosis requires both caspase and cathepsin activity. J. Immunol. 163:2478.
Li, L., and Y. S. Choi. 2002. Follicular dendritic cell-signaling molecules required for proliferation and differentiation of GC-B cells. Semin. Immunol. 14:259.
Wu, J., D. Qin, G. F. Burton, A. K. Szakal, and J. G. Tew. 1996. Follicular dendritic cell-derived antigen and accessory activity in initiation of memory IgG responses in vitro. J. Immunol. 157:3404.
Thielen, C., N. Antoine, F. Melot, J. Y. Cesbron, E. Heinen, and R. Tsunoda. 2001. Human FDC express PrPc in vivo and in vitro. Dev. Immunol. 8:259.
Li, C., and W. H. Wong. 2001. Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc. Natl. Acad. Sci. USA 98:31.
Tusher, V. G., R. Tibshirani, and G. Chu. 2001. Significance analysis of microarrays applied to the ionizing radiation response. Proc. Natl. Acad. Sci. USA 98:5116.
Fehr, T., R. C. Rickert, B. Odermatt, J. Roes, K. Rajewsky, H. Hengartner, and R. M. Zinkernagel. 1998. Antiviral protection and germinal center formation, but impaired B cell memory in the absence of CD19. J. Exp. Med. 188:145.
Wilson, M. R., and S. B. Easterbrook-Smith. 1992. Clusterin binds by a multivalent mechanism to the Fc and Fab regions of IgG. Biochim. Biophys. Acta 1159:319.
Mackay, F., G. R. Majeau, P. Lawton, P. S. Hochman, and J. L. Browning. 1997. Lymphotoxin but not tumor necrosis factor functions to maintain splenic architecture and humoral responsiveness in adult mice. Eur. J. Immunol. 27:2033,
Mackay, F., and J. L. Browning. 1998. Turning off follicular dendritic cells. Nature 395:26.
Montrasio, F., R. Frigg, M. Glatzel, M. A. Klein, F. Mackay, A. Aguzzi, and C. Weissmann. 2000. Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science 288:1257.
Imal, Y., and M. Yamakawa. 1996. Morphology, function and pathology of follicular dendritic cells. Pathol. Int. 46:807.
Ehlers, S., C. Holscher, S. Scheu, C. Tertilt, T. Hehlgans, J. Suwinski, R. Endres, and K. Pfeffer. 2003. The lymphotoxin β receptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes. J. Immunol. 170:5210.
Heldin, C. H., and B. Westermark. 1999. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev. 79:1283.
Leask, A., and D. J. Abraham. 2003. The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology. Biochem. Cell Biol. 81:355.
Fromigue, O., P. J. Marie, and A. Lomri. 1998. Bone morphogenetic protein-2 and transforming growth factor-β2 interact to modulate human bone marrow stromal cell proliferation and differentiation. J. Cell. Biochem. 68:411.
McBride, P. A., P. Eikelenboom, G. Kraal, H. Fraser, and M. E. Bruce. 1992. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice. J. Pathol. 168:413.
Hanayama, R., M. Tanaka, K. Miyasaka, K. Aozasa, M. Koike, Y. Uchiyama. and S, Nagata. 2004. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304:1147.
Erickson, S. L., F. J. de Sauvage, K. Kikly, K. Carver-Moore, S. Pitts-Meek, N. Gillett, K. C. Sheehan, R. D. Schreiber, D. V. Goeddel, and M. W. Moore. 1994. Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF rcecptor-2-deficient mice. Nature 372:560.
Le Hir, M., H. Bluethmann, M. H. Kosco-Vilbois, M. Muller, F. di Padova, M. Moore, B. Ryffel, and H. P. Eugster. 1995. Tumor necrosis factor receptor-1 signaling is required for differentiation of follicular dendritic cells, germinal center formation, and full antibody responses. J. Inflamm. 47:76.
Umezu-Goto, M., Y. Kishi, A. Taira, K. Hama, N. Dohmae, K. Takio, T. Yamori, G. B. Mills, K. Inoue, J. Aoki, and H. Arai. 2002. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic-acid production. J. Cell Biol. 158:227.
MacLennan, I. C. 1994. Germinal centers. Annu. Rev. Immunol. 12:117.
Liu, Y. J., D. E. Joshua, G. T. Williams, C. A. Smith, J. Gordon, and I. C. MacLennan. 19S9. Mechanism of antigen-driven selection in germinal centres. Nature 342:929.
Dejardin, E., N. M. Droin, M. Delhase, E. Haas, Y. Cao, C. Makris, Z. W. Li, M. Karin, C. F. Ware, and D. R. Green. 2002. The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity 17:525.
Ansel, K. M., V. N. Ngo, P. L. Hyman, S. A. Luther, R. Forster, J. D. Sedgwick, J. L. Browning, M. Lipp, and J. G. Cyster. 2000. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406:309.
Bromley, S. K., D. A. Peterson, M. D. Gunn, and M. L. Dustin. 2000. Cutting edge: hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation. J. Immunol. 165:15.
Bleul, C. C., R. C. Fuhlbrigge, J. M. Casasnovas, A. Aiuti, and T. A. Springer. 1996. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J. Exp. Med. 184:1101.
Lu, B., B. J. Rutledge, L. Gu, J. Fiorillo, N. W. Lukacs, S. L. Kunkel, R. North, C. Gerard, and B. J. Rollins. 1998. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J. Exp. Med. 187:601.
Koopman, G., H. K. Parmentier, H. J. Schuurman, W. Newman, C. J. Meijer, and S. T. Pals. 1991. Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and very late antigen 4/vascular cell adhesion molecule 1 pathways. J. Exp. Med. 173:1297.
Postigo, A. A., M. Marazuela, F. Sanchez-Madrid, and M. O. de Landazuri. 1994. B lymphocyte binding to E- and P-selectins is mediated through the de novo expression of carbohydrates on in vitro and in vivo activated human B cells. J. Clin. Invest. 94:1585.
Leuker, C. E., M. Labow, W. Muller, and N. Wagner. 2001. Neonatally induced inactivation of the vascular cell adhesion molecule 1 gene impairs B cell localization and T cell-dependent humoral immune response. J. Exp. Med. 193:755.
Hwang, S. T., M. S. Singer, P. A. Giblin, T. A. Yednock, K. B. Bacon, S. I. Simon, and S. D. Rosen. 1996. GlyCAM-1, a physiologic ligand for L-selectin, activates β2 integrins on naive peripheral lymphocytes. J. Exp. Med. 184:1343.
Oritani, K., and P. W. Kincade. 1996. Identification of stromal cell products that interact with pre-B cells. J. Cell Biol. 134:771.
Ruegg, C. R., R. Chiquet-Ehrismann, and S. S. Alkan. 1989. Tenascin, an extracellular matrix protein, exerts immunomodulatory activities. Proc. Natl. Acad. Sci. USA 86:7437.
Shakhov, A. N., I. G. Lyakhov, A. V. Tumanov, A. V. Rubtsov, L. N. Drutskaya, M. W. Marino, and S. A. Nedospasov. 2000. Gene profiling approach in the analysis of lymphotoxin and TNF deficiencies. J. Leukocyte Biol. 68:151.
Tumanov, A. V., D. V. Kuprash, and S. A. Nedospasov. 2003. The role of lymphotoxin in development and maintenance of secondary lymphoid tissues. Cytokine Growth Factor Rev. 14:275.
Jeannin, P., S. Lecoanet-Hencboz, Y. Delneste, J. F. Gauchat, and J. Y. Bonnefoy. 1998. α-1 antitrypsin up-regulates human B cell differentiation selectively into IgE- and IgG4-secreting cells. Eur. J. Immunol. 28:1815.
Zhang, X., L. Li, J. Jung, S. Xiang, C. Hollmann, and Y. S. Choi. 2001. The distinct roles of T cell-derived cytokines and a novel follicular dendritic cell-signaling molecule 8D6 in germinal center-B cell differentiation. J. Immunol. 167:49.
Haase, A. T., K. Henry, M. Zupancie, G. Sedgewick, R. A. Faust, H. Melroe, W. Cavert, K. Gebhard, K. Staskus, Z. Q. Zhang, et al. 1996. Quantitative image analysis of HIV-1 infection in lymphoid tissue. Science 274:985.
Kitamoto, T., T. Muramoto, S. Mohri, K. Doh ura, and J. Tateishi. 1991. Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease. J. Virol. 65:6292.
Hill, A. F., M. Zoidler, J. Ironside, and J. Collinge. 1997. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 349:99.
Glatzel, M., E. Abela, M. Maissen, and A. Aguzzi. 2003. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N. Engl. J. Med. 349:1812.
