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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 contribution
posted on 2023-05-17, 07:44 authored by Ngo, VN, Heinrich KornerHeinrich Korner, Gunn, MD, Schmidt, KN, Riminton, DS, Cooper, MD, Browning, JL, Sedgwick, JD, Cyster, JG
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.


Publication title

The Journal of Experimental Medicine








Menzies Institute for Medical Research


Rockefeller Univ Press

Place of publication

1114 First Ave, 4Th Fl, New York, USA, Ny, 10021

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Clinical health not elsewhere classified

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