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.
Journal Article (Journal Article)
Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta 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)-, LTalpha- and LTbeta-deficient mice. Treatment of adult mice with antagonists of LTalpha1beta2 also leads to decreased BLC expression. These findings indicate that LTalpha1beta2 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 LTalpha-, and LTbeta-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 LTalpha1beta2 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.
Full Text
Duke Authors
Cited Authors
- Ngo, VN; Korner, H; Gunn, MD; Schmidt, KN; Riminton, DS; Cooper, MD; Browning, JL; Sedgwick, JD; Cyster, JG
Published Date
- January 18, 1999
Published In
Volume / Issue
- 189 / 2
Start / End Page
- 403 - 412
PubMed ID
- 9892622
Pubmed Central ID
- PMC2192983
International Standard Serial Number (ISSN)
- 0022-1007
Digital Object Identifier (DOI)
- 10.1084/jem.189.2.403
Language
- eng
Conference Location
- United States