Role of TNF ligand and receptor family in the lymphoid organogenesis defined by gene targeting.
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.
Matsumoto
M
M
Division of Informative Cytology, University of Tokushima, Japan.
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D018390:Gene Targeting; D008024:Ligands; D008221:Lymphoid Tissue / Q000196:embryology*; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D015703:Antigens, CD; D008024:Ligands; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha