J. Exp. Med., Volume 187, Number 7, April 6, 1998 997-1007

The Sequential Role of Lymphotoxin and B Cells in the Development of Splenic Follicles

By Mercedes Gonzalez,^* Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois,^§ and Randolph J. Noelle^*

From the ^* Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756; the  Department of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142; and the ^§ Serono Pharmaceutical Research Institute, CH-1228 Plan-les-Ouates, Geneva, Switzerland

The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT- receptor (LT-R), since blocking ligand-receptor interaction in recipient SCID mice ablates the capacity of the transferred cells to segregate. A week after lymphocyte transfer, host-derived FDCs appeared in the reconstituted SCID mice. This induction of FDCs is dependent on LT-R signaling by B cells since LT-^/ B cells are incapable of inducing development of FDCs in SCID mice, even after cotransfer of LT-^+/+ T cells. Therefore, LT plays at least two discrete roles in splenic organization. First, it appears that LT induces the differentiation of the white pulp to create sites for lymphocyte segregation. Second, LT expression by B cells drives the maturation of FDCs and the organization of B cell follicles.

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

This article has been cited by other articles:

• Duddy, M., Niino, M., Adatia, F., Hebert, S., Freedman, M., Atkins, H., Kim, H. J., Bar-Or, A. (2007). Distinct Effector Cytokine Profiles of Memory and Naive Human B Cell Subsets and Implication in Multiple Sclerosis. J. Immunol. 178: 6092-6099 [Abstract] [Full Text]  
• Sun, Y., Blink, S. E., Chen, J. H., Fu, Y.-X. (2005). Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling. J. Immunol. 175: 884-890 [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]  
• Brown, G. R., Lee, E. L., El-Hayek, J., Kintner, K., Luck, C. (2005). IL-12-Independent LIGHT Signaling Enhances MHC Class II Disparate CD4+ T Cell Alloproliferation, IFN-{gamma} Responses, and Intestinal Graft-versus-Host Disease. J. Immunol. 174: 4688-4695 [Abstract] [Full Text]  
• Heikenwalder, M., Zeller, N., Seeger, H., Prinz, M., Klohn, P.-C., Schwarz, P., Ruddle, N. H., Weissmann, C., Aguzzi, A. (2005). Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions. Science 307: 1107-1110 [Abstract] [Full Text]  
• Basso, K., Klein, U., Niu, H., Stolovitzky, G. A., Tu, Y., Califano, A., Cattoretti, G., Dalla-Favera, R. (2004). Tracking CD40 signaling during germinal center development. Blood 104: 4088-4096 [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]  
• 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]  
• Hebeis, B. J., Klenovsek, K., Rohwer, P., Ritter, U., Schneider, A., Mach, M., Winkler, T. H. (2004). Activation of Virus-specific Memory B Cells in the Absence of T Cell Help. J. Exp. Med. 199: 593-602 [Abstract] [Full Text]  
• Vora, K. A., Wang, L. C., Rao, S. P., Liu, Z.-Y., Majeau, G. R., Cutler, A. H., Hochman, P. S., Scott, M. L., Kalled, S. L. (2003). Cutting Edge: Germinal Centers Formed in the Absence of B Cell-Activating Factor Belonging to the TNF Family Exhibit Impaired Maturation and Function. J. Immunol. 171: 547-551 [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]  
• 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]  
• 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]  
• Magez, S., Stijlemans, B., Caljon, G., Eugster, H.-P., De Baetselier, P. (2002). Control of Experimental Trypanosoma brucei Infections Occurs Independently of Lymphotoxin-{alpha} Induction. Infect. Immun. 70: 1342-1351 [Abstract] [Full Text]  
• Muller, S., Hunziker, L., Enzler, S., Buhler-Jungo, M., Di Santo, J. P., Zinkernagel, R. M., Mueller, C. (2002). Role of an Intact Splenic Microarchitecture in Early Lymphocytic Choriomeningitis Virus Production. J. Virol. 76: 2375-2383 [Abstract] [Full Text]  
• Dadgostar, H., Zarnegar, B., Hoffmann, A., Qin, X.-F., Truong, U., Rao, G., Baltimore, D., Cheng, G. (2002). Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes. Proc. Natl. Acad. Sci. USA 99: 1497-1502 [Abstract] [Full Text]  
• Youinou, P, Lydyard, P M, Mageed, R A (2002). B cells underpin lupus immunopathology. Lupus 11: 1-3  
• Ngo, V. N., Cornall, R. J., Cyster, J. G. (2001). Splenic T Zone Development Is B Cell Dependent. J. Exp. Med. 194: 1649-1660 [Abstract] [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]  
• 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]  
• Hashi, H., Yoshida, H., Honda, K., Fraser, S., Kubo, H., Awane, M., Takabayashi, A., Nakano, H., Yamaoka, Y., Nishikawa, S.-I. (2001). Compartmentalization of Peyer's Patch Anlagen Before Lymphocyte Entry. J. Immunol. 166: 3702-3709 [Abstract] [Full Text]  
• Montrasio, F., Cozzio, A., Flechsig, E., Rossi, D., Klein, M. A., Rülicke, T., Raeber, A. J., Vosshenrich, C. A. J., Proft, J., Aguzzi, A., Weissmann, C. (2001). B lymphocyte-restricted expression of prion protein does not enable prion replication in prion protein knockout mice. Proc. Natl. Acad. Sci. USA 10.1073/pnas.051609398v1 [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]  
• Shi, K., Hayashida, K., Kaneko, M., Hashimoto, J., Tomita, T., Lipsky, P. E., Yoshikawa, H., Ochi, T. (2001). Lymphoid Chemokine B Cell-Attracting Chemokine-1 (CXCL13) Is Expressed in Germinal Center of Ectopic Lymphoid Follicles Within the Synovium of Chronic Arthritis Patients. J. Immunol. 166: 650-655 [Abstract] [Full Text]  
• Chen, C.-L., Singh, N., Yull, F. E., Strayhorn, D., Van Kaer, L., Kerr, L. D. (2000). Lymphocytes Lacking I{kappa}B-{alpha} Develop Normally, But Have Selective Defects in Proliferation and Function. J. Immunol. 165: 5418-5427 [Abstract] [Full Text]  
• Essen, D. v., Dullforce, P., Brocker, T., Gray, D. (2000). Cellular Interactions Involved in Th Cell Memory. J. Immunol. 165: 3640-3646 [Abstract] [Full Text]  
• Skinner, P. J., Daniels, M. A., Schmidt, C. S., Jameson, S. C., Haase, A. T. (2000). Cutting Edge: In Situ Tetramer Staining of Antigen-Specific T Cells in Tissues. J. Immunol. 165: 613-617 [Abstract] [Full Text]  
• Shinall, S. M., Gonzalez-Fernandez, M., Noelle, R. J., Waldschmidt, T. J. (2000). Identification of Murine Germinal Center B Cell Subsets Defined by the Expression of Surface Isotypes and Differentiation Antigens. J. Immunol. 164: 5729-5738 [Abstract] [Full Text]  
• Montrasio, F., Frigg, R., Glatzel, M., Klein, M. A., Mackay, F., Aguzzi, A., Weissmann, C. (2000). Impaired Prion Replication in Spleens of Mice Lacking Functional Follicular Dendritic Cells. Science 288: 1257-1259 [Abstract] [Full Text]  
• Fagarasan, S., Shinkura, R., Kamata, T., Nogaki, F., Ikuta, K., Tashiro, K., Honjo, T. (2000). Alymphoplasia (aly)-type Nuclear Factor {kappa}B-inducing Kinase (NIK) Causes Defects in Secondary Lymphoid Tissue Chemokine Receptor Signaling and Homing of Peritoneal Cells to the Gut-associated Lymphatic Tissue System. J. Exp. Med. 191: 1477-1486 [Abstract] [Full Text]  
• Li, L., Zhang, X., Kovacic, S., Long, A. J., Bourque, K., Wood, C. R., Choi, Y. S. (2000). Identification of a Human Follicular Dendritic Cell Molecule That Stimulates Germinal Center B Cell Growth. J. Exp. Med. 191: 1077-1084 [Abstract] [Full Text]  
• Choe, J., Li, L., Zhang, X., Gregory, C. D., Choi, Y. S. (2000). Distinct Role of Follicular Dendritic Cells and T Cells in the Proliferation, Differentiation, and Apoptosis of a Centroblast Cell Line, L3055. J. Immunol. 164: 56-63 [Abstract] [Full Text]  
• Wu, Q., Wang, Y., Wang, J., Hedgeman, E. O., Browning, J. L., Fu, Y.-X. (1999). The Requirement of Membrane Lymphotoxin for the Presence of Dendritic Cells in Lymphoid Tissues. J. Exp. Med. 190: 629-638 [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]  
• Ohshima, Y., Yang, L-P., Avice, M-N., Kurimoto, M., Nakajima, T., Sergerie, M., Demeure, C. E., Sarfati, M., Delespesse, G. (1999). Naive Human CD4+ T Cells Are a Major Source of Lymphotoxin {alpha}. J. Immunol. 162: 3790-3794 [Abstract] [Full Text]  
• HogenEsch, H., Janke, S., Boggess, D., Sundberg, J. P. (1999). Absence of Peyer's Patches and Abnormal Lymphoid Architecture in Chronic Proliferative Dermatitis (cpdm/cpdm) Mice. J. Immunol. 162: 3890-3896 [Abstract] [Full Text]  
• Raeber, A. J., Sailer, A., Hegyi, I., Klein, M. A., Rulicke, T., Fischer, M., Brandner, S., Aguzzi, A., Weissmann, C. (1999). Ectopic expression of prion protein (PrP) in T lymphocytes or hepatocytes of PrP knockout mice is insufficient to sustain prion replication. Proc. Natl. Acad. Sci. USA 96: 3987-3992 [Abstract] [Full Text]  
• Gramaglia, I., Mauri, D. N., Miner, K. T., Ware, C. F., Croft, M. (1999). Lymphotoxin {alpha}{beta} Is Expressed on Recently Activated Naive and Th1-Like CD4 Cells but Is Down-Regulated by IL-4 During Th2 Differentiation. J. Immunol. 162: 1333-1338 [Abstract] [Full Text]  
• Ngo, V. N., Korner, H., Gunn, M. D., Schmidt, K. N., Sean Riminton, D., Cooper, M. D., Browning, J. L., Sedgwick, J. D., Cyster, J. G. (1999). Lymphotoxin alpha /beta and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen. J. Exp. Med. 189: 403-412 [Abstract] [Full Text]  
• Endres, R., Alimzhanov, M. B., Plitz, T., Futterer, A., Kosco-Vilbois, M. H., Nedospasov, S. A., Rajewsky, K., Pfeffer, K. (1999). Mature Follicular Dendritic Cell Networks Depend on Expression of Lymphotoxin beta  Receptor by Radioresistant Stromal Cells and of Lymphotoxin beta  and Tumor Necrosis Factor by B Cells. J. Exp. Med. 189: 159-168 [Abstract] [Full Text]  
• Cook, M. C., Korner, H., Sean Riminton, D., Lemckert, F. A., Hasbold, J., Amesbury, M., Hodgkin, P. D., Cyster, J. G., Sedgwick, J. D., Basten, A. (1998). Generation of Splenic Follicular Structure and B Cell Movement in Tumor Necrosis Factor-deficient Mice. J. Exp. Med. 188: 1503-1510 [Abstract] [Full Text]  
• Montrasio, F., Cozzio, A., Flechsig, E., Rossi, D., Klein, M. A., Rulicke, T., Raeber, A. J., Vosshenrich, C. A. J., Proft, J., Aguzzi, A., Weissmann, C. (2001). B lymphocyte-restricted expression of prion protein does not enable prion replication in prion protein knockout mice. Proc. Natl. Acad. Sci. USA 98: 4034-4037 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS