SELECTIVE DISRUPTION OF LYMPHOTOXIN LIGANDS REVEALS A NOVEL SET OF MUCOSAL LYMPH-NODES AND UNIQUE EFFECTS ON LYMPH-NODE CELLULAR-ORGANIZATION

Lymphotoxin (LT) provides a critical signal for the genesis of lymph n odes (LN) in mice, Here we show that mice treated in utero with LT bet a-R-IQ, which binds to the membrane LT alpha 1 beta 2 heterotrimer, la cked most LN, yet retained a set of mucosal surface draining LN, Since mice genetically deficient in LT alpha lack all LN, including the muc osal set, we hypothesize that a novel LT alpha-dependent pathway contr ols their genesis. This novel set of mucosal LN cannot be discriminate d on the basis of addressin expression, The discovery of LN in mice tr eated with LT beta-R-Ig fusion protein in utero allowed us to compare the roles of membrane LT alpha beta or soluble LT alpha/tumor necrosis factor (TNF) in the development of cellular organization in LN and sp leen. Our results indicate that both membrane LT alpha beta and solubl e LT alpha/TNF mediate T-B cell segregation and the organization of a cell follicles in spleen and LN. Interestingly, while antagonism of me mbrane LT alpha beta or soluble LT alpha/TNF prevented germinal center (GC) formation in spleen, antagonism of soluble LT alpha/TNF had no e ffect on LN formation, The data suggest that multiple LT/TNF ligands c ontrol a cell follicle organization in the spleen and LN of adult mice , and that the requirements for LT/TNF ligands in GC formation are dis tinct in the different lymphoid organs.