Lymph node genesis is induced by signaling through the lymphotoxin β receptor

We investigated lymphotoxin (LT) and TNF function in lymph node genesis and cellular organization by manipulating LT beta-R and TNF-R signaling. 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 can develop independently of LT alpha beta/LT beta-R interaction were generated. Normal mice treated in utero with LT beta-R-Ig and TNF-R55-Ig or anti-TNF lacked all lymph nodes, indicating that TNF signaling contributes to lymph node genesis. Lymph nodes generated in LT alpha(-/-) mice had disrupted cellular organization. Therefore, LT beta-R signaling during gestation is not sufficient to establish normal cellular microarchitecture. We conclude that LT and TNF play critical roles in the genesis and cellular organization of lymph nodes.