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J. Exp. Med.,
Volume 189, Number 2, January 18, 1999 403-412
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and Tumor Necrosis Factor Are
Required for Stromal Cell Expression of Homing
Chemokines in B and T Cell Areas of the Spleen
By


§
From the * Department of Microbiology and Immunology, and Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT)
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
/
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)-, LT
- and LT
-deficient mice. Treatment of adult mice with antagonists of LT
1
2 also leads to decreased BLC expression. These findings indicate that LT
1
2 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 LT
-, and LT
-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 LT
1
2 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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