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J Med Invest. 1999 Aug;46(3-4):141-50.

Role of TNF ligand and receptor family in the lymphoid organogenesis defined by gene targeting.

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  • 1Division of Informative Cytology, University of Tokushima, Japan.

Abstract

The molecular basis of lymphoid organogenesis has recently been elucidated using gene-targeted mice. Mice deficient in lymphotoxin-alpha (LT alpha) lack lymph nodes and Peyer's patches. The action of LT alpha in lymphoid organogenesis is mediated mostly by the membrane form of LT by a mechanism independent of TNF receptor I (TNFR-I) or II (TNFR-II). Additionally, follicular dendritic cell (FDC) clusters or germinal centers fail to develop in the spleen of LT alpha-deficient mice. Mice deficient in either TNFR-I or LT beta R also fail to develop splenic FDC clusters and germinal centers, indicating that signaling through both TNFR-I and LT beta R is required for the development of these structures. The mechanisms underlying the defective lymphoid organogenesis in LT alpha-deficient mice, together with a natural mutant strain, alymphoplasia (aly) mice, which manifest a quite similar phenotype to LT alpha-deficient mice, were investigated by generating aggregation chimeras. These studies demonstrate that LT alpha and the aly gene product together control lymphoid organogenesis with a close mechanistic relationship in their biochemical pathways through governing distinct cellular compartments; the former acting as a circulating ligand and the latter as a LT beta R-signaling molecule expressed by the stroma of the lymphoid organs.

PMID:
10687308
[PubMed - indexed for MEDLINE]
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