Role of TNF Ligand and Receptor Family in the Lymphoid Organogenesis Defined by Gene Targeting

概要

論文の詳細を見る
The molecular basis of lymphoid organogenesis has recently been elucidated using gene-targeted mice. Mice deficient in lymphotoxin-α (LTα) lack lymph nodes and Peyer's patches. The action of LTα 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 LTα-deficient mice. Mice deficient in either TNFR-I or LTβR also fail to develop splenic FDC clusters and germinal centers, indicating that signaling through both TNFR-I and LTβR is required for the development of these structures. The mechanisms underlying the defective lymphoid organogenesis in LTα-deficient mice, together with a natural mutant strain, alymphoplasia (aly) mice, which manifest a quite similar phenotype to LTα-deficient mice, were investigated by generating aggregation chimeras. These studies demonstrate that LTα 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 LTβR-signaling molecule expressed by the stroma of the lymphoid organs.
徳島大学の論文