LYMPH-NODE GENESIS IS INDUCED BY SIGNALING THROUGH THE LYMPHOTOXIN BETA-RECEPTOR

We investigated lymphotoxin (LT) and TNF function in lymph node genesi s and cellular organization by manipulating LT beta-R and TNF-R signal ing. Lymph nodes developed in LT alpha(-/-) mice treated in utero with agonist anti-LT beta-R monoclonal antibody. Thus, LT beta-R signaling mediates lymph node genesis. Surprisingly, mucosal lymph nodes that c an develop independently of LT alpha beta/LT beta-R interaction were g enerated. Normal mice treated in utero with LT beta-R-Ig and TNF-R55-I g or anti-TNF lacked all lymph nodes, indicating that TNF signaling co ntributes to lymph node genesis. Lymph nodes generated in LT alpha(-/- ) mice had disrupted cellular organization. Therefore, LT beta-R signa ling during gestation is not sufficient to establish normal cellular m icroarchitecture. We conclude that LT and TNF play critical roles in t he genesis and cellular organization of lymph nodes.