J. Exp. Med., Volume 189, Number 1, January 4, 1999 159-168

Mature Follicular Dendritic Cell Networks Depend on Expression of Lymphotoxin  Receptor by Radioresistant Stromal Cells and of Lymphotoxin  and Tumor Necrosis Factor by B Cells

By Robert Endres,^* Marat B. Alimzhanov, Thomas Plitz,^* Agnes Fütterer,^* Marie H. Kosco-Vilbois,^§ Sergei A. Nedospasov, Klaus Rajewsky, and Klaus Pfeffer^*

From the ^* Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, D-81675 Munich, Germany; the  Institute for Genetics, University of Cologne, D-50931 Cologne, Germany; ^§ Serono Pharmaceutical Research Institute, Plan-les-Ouates, CH-1228, Switzerland; and the  Engelhardt Institute of Molecular Biology and Belozersky Institute of Physico-Chemical Biology, 117984 Moscow, Russia

The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF), lymphotoxin (LT) , and LT, as well as their receptors TNF receptor p55 (TNFRp55) and LTR play essential roles in the development of GCs. To establish in which cell types expression of LTR, LT, and TNF is required for GC formation, LTR^/, LT^/, TNF^/, B cell-deficient (BCR^/), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice. GCs, herein defined as peanut agglutinin-binding (PNA⁺) clusters of centroblasts/centrocytes in association with follicular dendritic cell (FDC) networks, were not detectable in LTR^/ hosts after transfer of wild-type BM. In contrast, the GC reaction was restored in LT^/ hosts reconstituted with either wild-type or LTR^/ BM. In BCR^/ recipients reconstituted with compound LT^//BCR^/ or TNF^//BCR^/ BM grafts, PNA⁺ cell clusters formed in splenic follicles, but associated FDC networks were strongly reduced or absent. Thus, development of splenic FDC networks depends on expression of LT and TNF by B lymphocytes and LTR by radioresistant stromal cells.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Grabner, R., Lotzer, K., Dopping, S., Hildner, M., Radke, D., Beer, M., Spanbroek, R., Lippert, B., Reardon, C. A., Getz, G. S., Fu, Y.-X., Hehlgans, T., Mebius, R. E., van der Wall, M., Kruspe, D., Englert, C., Lovas, A., Hu, D., Randolph, G. J., Weih, F., Habenicht, A. J.R. (2009). Lymphotoxin {beta} receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. JEM 206: 233-248 [Abstract] [Full Text]  
• Ehrchen, J. M., Roth, J., Roebrock, K., Varga, G., Domschke, W., Newberry, R., Sorg, C., Muller-Tidow, C., Sunderkotter, C., Kucharzik, T., Spahn, T. W. (2008). The Absence of Cutaneous Lymph Nodes Results in a Th2 Response and Increased Susceptibility to Leishmania major Infection in Mice. Infect. Immun. 76: 4241-4250 [Abstract] [Full Text]  
• Cantaert, T., Kolln, J., Timmer, T., van der Pouw Kraan, T. C., Vandooren, B., Thurlings, R. M., Canete, J. D., Catrina, A. I., Out, T., Verweij, C. L., Zhang, Y., Tak, P. P., Baeten, D. (2008). B Lymphocyte Autoimmunity in Rheumatoid Synovitis Is Independent of Ectopic Lymphoid Neogenesis. J. Immunol. 181: 785-794 [Abstract] [Full Text]  
• Steinberg, M. W., Turovskaya, O., Shaikh, R. B., Kim, G., McCole, D. F., Pfeffer, K., Murphy, K. M., Ware, C. F., Kronenberg, M. (2008). A crucial role for HVEM and BTLA in preventing intestinal inflammation. JEM 205: 1463-1476 [Abstract] [Full Text]  
• Zarnegar, B., Yamazaki, S., He, J. Q., Cheng, G. (2008). Control of canonical NF-{kappa}B activation through the NIK-IKK complex pathway. Proc. Natl. Acad. Sci. USA 105: 3503-3508 [Abstract] [Full Text]  
• Vu, F., Dianzani, U., Ware, C. F., Mak, T., Gommerman, J. L. (2008). ICOS, CD40, and Lymphotoxin {beta} Receptors Signal Sequentially and Interdependently to Initiate a Germinal Center Reaction. J. Immunol. 180: 2284-2293 [Abstract] [Full Text]  
• Murakami, T., Chen, X., Hase, K., Sakamoto, A., Nishigaki, C., Ohno, H. (2007). Splenic CD19 CD35+B220+ cells function as an inducer of follicular dendritic cell network formation. Blood 110: 1215-1224 [Abstract] [Full Text]  
• Al-Alwan, M., Du, Q., Hou, S., Nashed, B., Fan, Y., Yang, X., Marshall, A. J. (2007). Follicular Dendritic Cell Secreted Protein (FDC-SP) Regulates Germinal Center and Antibody Responses. J. Immunol. 178: 7859-7867 [Abstract] [Full Text]  
• Thai, T.-H., Calado, D. P., Casola, S., Ansel, K. M., Xiao, C., Xue, Y., Murphy, A., Frendewey, D., Valenzuela, D., Kutok, J. L., Schmidt-Supprian, M., Rajewsky, N., Yancopoulos, G., Rao, A., Rajewsky, K. (2007). Regulation of the Germinal Center Response by MicroRNA-155. Science 316: 604-608 [Abstract] [Full Text]  
• Natkunam, Y. (2007). The Biology of the Germinal Center. ASH Education Book 2007: 210-215 [Abstract] [Full Text]  
• Nishikawa, Y., Hikida, M., Magari, M., Kanayama, N., Mori, M., Kitamura, H., Kurosaki, T., Ohmori, H. (2006). Establishment of Lymphotoxin beta Receptor Signaling-Dependent Cell Lines with Follicular Dendritic Cell Phenotypes from Mouse Lymph Nodes. J. Immunol. 177: 5204-5214 [Abstract] [Full Text]  
• Sukumar, S., Conrad, D. H., Szakal, A. K., Tew, J. G. (2006). Differential T Cell-Mediated Regulation of CD23 (Fc{epsilon}RII) in B Cells and Follicular Dendritic Cells.. J. Immunol. 176: 4811-4817 [Abstract] [Full Text]  
• Lo, J. C., Basak, S., James, E. S., Quiambo, R. S., Kinsella, M. C., Alegre, M.-L., Weih, F., Franzoso, G., Hoffmann, A., Fu, Y.-X. (2006). Coordination between NF-{kappa}B family members p50 and p52 is essential for mediating LTbetaR signals in the development and organization of secondary lymphoid tissues. Blood 107: 1048-1055 [Abstract] [Full Text]  
• Wen, L., Shinton, S. A., Hardy, R. R., Hayakawa, K. (2005). Association of B-1 B Cells with Follicular Dendritic Cells in Spleen. J. Immunol. 174: 6918-6926 [Abstract] [Full Text]  
• Mortarini, R., Scarito, A., Nonaka, D., Zanon, M., Bersani, I., Montaldi, E., Pennacchioli, E., Patuzzo, R., Santinami, M., Anichini, A. (2005). Constitutive Expression and Costimulatory Function of LIGHT/TNFSF14 on Human Melanoma Cells and Melanoma-Derived Microvesicles. Cancer Res. 65: 3428-3436 [Abstract] [Full Text]  
• Mohan, J., Bruce, M. E., Mabbott, N. A. (2005). Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells. J. Virol. 79: 1888-1897 [Abstract] [Full Text]  
• Cupedo, T., Lund, F. E., Ngo, V. N., Randall, T. D., Jansen, W., Greuter, M. J., de Waal-Malefyt, R., Kraal, G., Cyster, J. G., Mebius, R. E. (2004). Initiation of Cellular Organization in Lymph Nodes Is Regulated by Non-B Cell-Derived Signals and Is Not Dependent on CXC Chemokine Ligand 13. J. Immunol. 173: 4889-4896 [Abstract] [Full Text]  
• Cox, R. A., Magee, D. M. (2004). Coccidioidomycosis: Host Response and Vaccine Development. Clin. Microbiol. Rev. 17: 804-839 [Abstract] [Full Text]  
• Tumanov, A. V., Kuprash, D. V., Mach, J. A., Nedospasov, S. A., Chervonsky, A. V. (2004). Lymphotoxin and TNF Produced by B Cells Are Dispensable for Maintenance of the Follicle-Associated Epithelium but Are Required for Development of Lymphoid Follicles in the Peyer's Patches. J. Immunol. 173: 86-91 [Abstract] [Full Text]  
• Voon, D. C., Subrata, L. S., Karimi, M., Ulgiati, D., Abraham, L. J. (2004). TNF and Phorbol Esters Induce Lymphotoxin-{beta} Expression through Distinct Pathways Involving Ets and NF-{kappa}B Family Members. J. Immunol. 172: 4332-4341 [Abstract] [Full Text]  
• Park, S.-M., Park, H.-Y., Lee, T. H. (2003). Functional Effects of TNF-{alpha} on a Human Follicular Dendritic Cell Line: Persistent NF-{kappa}B Activation and Sensitization for Fas-Mediated Apoptosis. J. Immunol. 171: 3955-3962 [Abstract] [Full Text]  
• Endres, R., Hacker, G., Brosch, I., Pfeffer, K. (2003). Apparently Normal Tumor Necrosis Factor Receptor 1 Signaling in the Absence of the Silencer of Death Domains. Mol. Cell. Biol. 23: 6609-6617 [Abstract] [Full Text]  
• Boehm, T., Scheu, S., Pfeffer, K., Bleul, C. C. (2003). Thymic Medullary Epithelial Cell Differentiation, Thymocyte Emigration, and the Control of Autoimmunity Require Lympho-Epithelial Cross Talk via LT{beta}R. JEM 198: 757-769 [Abstract] [Full Text]  
• Fava, R. A., Notidis, E., Hunt, J., Szanya, V., Ratcliffe, N., Ngam-ek, A., de Fougerolles, A. R., Sprague, A., Browning, J. L. (2003). A Role for the Lymphotoxin/LIGHT Axis in the Pathogenesis of Murine Collagen-Induced Arthritis. J. Immunol. 171: 115-126 [Abstract] [Full Text]  
• Mabbott, N. A., Young, J., McConnell, I., Bruce, M. E. (2003). Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility. J. Virol. 77: 6845-6854 [Abstract] [Full Text]  
• Aguzzi, A., Heppner, F. L, Heikenwalder, M., Prinz, M., Mertz, K., Seeger, H., Glatzel, M. (2003). Immune system and peripheral nerves in propagation of prions to CNS. Br Med Bull 66: 141-159 [Abstract] [Full Text]  
• Bell, J., Gray, D. (2003). Antigen-capturing Cells Can Masquerade as Memory B Cells. JEM 197: 1233-1244 [Abstract] [Full Text]  
• Ehlers, S., Holscher, C., Scheu, S., Tertilt, C., Hehlgans, T., Suwinski, J., Endres, R., Pfeffer, K. (2003). The Lymphotoxin {beta} Receptor Is Critically Involved in Controlling Infections with the Intracellular Pathogens Mycobacterium tuberculosis and Listeria monocytogenes. J. Immunol. 170: 5210-5218 [Abstract] [Full Text]  
• Prinz, M., Huber, G., Macpherson, A. J. S., Heppner, F. L., Glatzel, M., Eugster, H.-P., Wagner, N., Aguzzi, A. (2003). Oral Prion Infection Requires Normal Numbers of Peyer's Patches but Not of Enteric Lymphocytes. Am. J. Pathol. 162: 1103-1111 [Abstract] [Full Text]  
• Pihlgren, M., Tougne, C., Bozzotti, P., Fulurija, A., Duchosal, M. A., Lambert, P.-H., Siegrist, C.-A. (2003). Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens. J. Immunol. 170: 2824-2832 [Abstract] [Full Text]  
• Hu, H.-M., Winter, H., Ma, J., Croft, M., Urba, W. J., Fox, B. A. (2002). CD28, TNF Receptor, and IL-12 Are Critical for CD4-Independent Cross-Priming of Therapeutic Antitumor CD8+ T Cells. J. Immunol. 169: 4897-4904 [Abstract] [Full Text]  
• Marshall, A. J., Du, Q., Draves, K. E., Shikishima, Y., HayGlass, K. T., Clark, E. A. (2002). FDC-SP, a Novel Secreted Protein Expressed by Follicular Dendritic Cells. J. Immunol. 169: 2381-2389 [Abstract] [Full Text]  
• Warnatz, K., Denz, A., Drager, R., Braun, M., Groth, C., Wolff-Vorbeck, G., Eibel, H., Schlesier, M., Peter, H. H. (2002). Severe deficiency of switched memory B cells (CD27+IgM-IgD-) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood 99: 1544-1551 [Abstract] [Full Text]  
• Alcamo, E., Hacohen, N., Schulte, L. C., Rennert, P. D., Hynes, R. O., Baltimore, D. (2002). Requirement for the NF-{kappa}B Family Member RelA in the Development of Secondary Lymphoid Organs. JEM 195: 233-244 [Abstract] [Full Text]  
• Huang, F.-P., Farquhar, C. F., Mabbott, N. A., Bruce, M. E., MacPherson, G. G. (2002). Migrating intestinal dendritic cells transport PrPSc from the gut. J. Gen. Virol. 83: 267-271 [Abstract] [Full Text]  
• Ngo, V. N., Cornall, R. J., Cyster, J. G. (2001). Splenic T Zone Development Is B Cell Dependent. JEM 194: 1649-1660 [Abstract] [Full Text]  
• Mabbott, N. A., Bruce, M. E. (2001). The immunobiology of TSE diseases. J. Gen. Virol. 82: 2307-2318 [Full Text]  
• Weyand, C. M., Kurtin, P. J., Goronzy, J. J. (2001). Ectopic Lymphoid Organogenesis : A Fast Track for Autoimmunity. Am. J. Pathol. 159: 787-793 [Full Text]  
• Dohi, T., Rennert, P. D., Fujihashi, K., Kiyono, H., Shirai, Y., Kawamura, Y. I., Browning, J. L., McGhee, J. R. (2001). Elimination of Colonic Patches with Lymphotoxin {beta} Receptor-Ig Prevents Th2 Cell-Type Colitis. J. Immunol. 167: 2781-2790 [Abstract] [Full Text]  
• Weih, D. S., Yilmaz, Z. B., Weih, F. (2001). Essential Role of RelB in Germinal Center and Marginal Zone Formation and Proper Expression of Homing Chemokines. J. Immunol. 167: 1909-1919 [Abstract] [Full Text]  
• Zhang, X., Li, L., Jung, J., Xiang, S., Hollmann, C., Choi, Y. S. (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: 49-56 [Abstract] [Full Text]  
• Rennert, P. D., Hochman, P. S., Flavell, R. A., Chaplin, D. D., Jayaraman, S., Browning, J. L., Fu, Y.-X. (2001). Essential Role of Lymph Nodes in Contact Hypersensitivity Revealed in Lymphotoxin-{alpha}-deficient Mice. JEM 193: 1227-1238 [Abstract] [Full Text]  
• Honda, K., Nakano, H., Yoshida, H., Nishikawa, S., Rennert, P., Ikuta, K., Tamechika, M., Yamaguchi, K., Fukumoto, T., Chiba, T., Nishikawa, S.-I. (2001). Molecular Basis for Hematopoietic/Mesenchymal Interaction during Initiation of Peyer's Patch Organogenesis. JEM 193: 621-630 [Abstract] [Full Text]  
• Wang, Y., Wang, J., Sun, Y., Wu, Q., Fu, Y.-X. (2001). Complementary Effects of TNF and Lymphotoxin on the Formation of Germinal Center and Follicular Dendritic Cells. J. Immunol. 166: 330-337 [Abstract] [Full Text]  
• Raman, V. S., Bal, V., Rath, S., George, A. (2000). Ligation of CD27 on Murine B Cells Responding to T-Dependent and T-Independent Stimuli Inhibits the Generation of Plasma Cells. J. Immunol. 165: 6809-6815 [Abstract] [Full Text]  
• Sun, Z., Unutmaz, D., Zou, Y.-R., Sunshine, M. J., Pierani, A., Brenner-Morton, S., Mebius, R. E., Littman, D. R. (2000). Requirement for RORgamma in Thymocyte Survival and Lymphoid Organ Development. Science 288: 2369-2373 [Abstract] [Full Text]  
• Qin, D., Wu, J., Vora, K. A., Ravetch, J. V., Szakal, A. K., Manser, T., Tew, J. G. (2000). Fc{gamma} Receptor IIB on Follicular Dendritic Cells Regulates the B Cell Recall Response. J. Immunol. 164: 6268-6275 [Abstract] [Full Text]  
• Fan, L., Reilly, C. R., Luo, Y., Dorf, M. E., Lo, D. (2000). Cutting Edge: Ectopic Expression of the Chemokine TCA4/SLC Is Sufficient to Trigger Lymphoid Neogenesis. J. Immunol. 164: 3955-3959 [Abstract] [Full Text]  
• Matsumoto, M., Iwamasa, K., Rennert, P. D., Yamada, T., Suzuki, R., Matsushima, A., Okabe, M., Fujita, S., Yokoyama, M. (1999). Involvement of Distinct Cellular Compartments in the Abnormal Lymphoid Organogenesis in Lymphotoxin-{alpha}-Deficient Mice and Alymphoplasia (aly) Mice Defined by the Chimeric Analysis. J. Immunol. 163: 1584-1591 [Abstract] [Full Text]  
• LITTMAN, D.R., SUN, Z., UNUTMAZ, D., SUNSHINE, M.J., PETRIE, H.T., ZOU, Y.-R. (1999). Role of the Nuclear Hormone Receptor ROR{gamma} in Transcriptional Regulation, Thymocyte Survival, and Lymphoid Organogenesis. Cold Spring Harb Symp Quant Biol 64: 373-382 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS