Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) α/β lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of splenic follicles. Here we report that BLC expression by follicular stromal cells is defective in TNF-, TNF receptor 1 (TNFR1)-, LTα- and LTβ-deficient mice. Treatment of adult mice with antagonists of LTα1β2 also leads to decreased BLC expression. These findings indicate that LTα1β2 and TNF have a role upstream of BLC/CXCR5 in the process of follicle formation. In addition to disrupted follicles, LT-deficient animals have disorganized T zones. Expression of the T cell attractant, secondary lymphoid tissue chemokine (SLC), by T zone stromal cells is found to be markedly depressed in LTα-, and LTβ-deficient mice. Expression of the SLC-related chemokine, Epstein Barr virus–induced molecule 1 ligand chemokine (ELC), is also reduced. Exploring the basis for the reduced SLC expression led to identification of further disruptions in T zone stromal cells. Together these findings indicate that LTα1β2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen.
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18 January 1999
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January 18 1999
Lymphotoxin α/β and Tumor Necrosis Factor Are Required for Stromal Cell Expression of Homing Chemokines in B and T Cell Areas of the Spleen
Vu N. Ngo,
Vu N. Ngo
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Heinrich Korner,
Heinrich Korner
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Michael D. Gunn,
Michael D. Gunn
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Kerstin N. Schmidt,
Kerstin N. Schmidt
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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D. Sean Riminton,
D. Sean Riminton
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Max D. Cooper,
Max D. Cooper
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Jeffrey L. Browning,
Jeffrey L. Browning
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Jonathon D. Sedgwick,
Jonathon D. Sedgwick
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Jason G. Cyster
Jason G. Cyster
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
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Vu N. Ngo
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Heinrich Korner
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Michael D. Gunn
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Kerstin N. Schmidt
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
D. Sean Riminton
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Max D. Cooper
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Jeffrey L. Browning
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Jonathon D. Sedgwick
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Jason G. Cyster
From the *Department of Microbiology and Immunology, and ‡Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; §Centenary Institute of Cancer Medicine and Cell Biology, Sydney, 2050 New South Wales, Australia; ‖Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294; and ¶Biogen Inc., Cambridge, Massachusetts 02142
Address correspondence to Jason G. Cyster, Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus St., San Francisco, CA 94143-0414. Phone: 415-502-6427; Fax: 415-502-8424; E-mail: [email protected]
J.D. Sedgwick, H. Korner, and D.S. Riminton were supported by grants from the National Health and Medical Research Council of Australia and the National Multiple Sclerosis Society of Australia. J.G. Cyster is a Pew Scholar in the biomedical sciences. This work was supported in part by National Institutes of Health grant AI40098 to J.G. Cyster and by Howard Hughes Medical Institute grant 76296-549901 to the University of California San Francisco School of Medicine.
J.D. Sedgwick's present address is DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304-1104.
Received:
September 09 1998
Revision Received:
November 04 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (2): 403–412.
Article history
Received:
September 09 1998
Revision Received:
November 04 1998
Citation
Vu N. Ngo, Heinrich Korner, Michael D. Gunn, Kerstin N. Schmidt, D. Sean Riminton, Max D. Cooper, Jeffrey L. Browning, Jonathon D. Sedgwick, Jason G. Cyster; Lymphotoxin α/β 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 18 January 1999; 189 (2): 403–412. doi: https://doi.org/10.1084/jem.189.2.403
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