Matsumoto, Mitsuru Division of Informative Cytology, Institute for Enzyme Research, University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
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.
The journal of medical investigation : JMI
LID201111172003.pdf 164 KB
Institute of Advanced Medical Sciences