Selective disruption of lymphotoxin ligands reveals a novel set of mucosal lymph nodes and unique effects on lymph node cellular organization

• Published in: International immunology 1997-11, Vol.9 (11), p.1627-1639
• Main Authors: Rennert, P D, Browning, J L, Hochman, P S
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - metabolism; Antigens, CD - physiology; Antigens, Surface - biosynthesis; B-Lymphocytes - cytology; CD58 Antigens - metabolism; CD58 Antigens - physiology; Down-Regulation; Female; Humans; Ligands; Lymph Nodes - cytology; Lymph Nodes - embryology; Lymph Nodes - metabolism; Lymphotoxin-alpha - antagonists & inhibitors; Lymphotoxin-alpha - metabolism; Lymphotoxin-alpha - physiology; Lymphotoxin-beta; Male; Membrane Proteins - metabolism; Membrane Proteins - physiology; Mice; Mice, Inbred BALB C; Mucous Membrane - embryology; Pregnancy; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor - physiology; Receptors, Tumor Necrosis Factor, Type I; T-Lymphocytes - cytology; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/9.11.1627

Lymphotoxin (LT) provides a critical signal for the genesis of lymph nodes (LN) in mice. Here we show that mice treated in utero with LT beta-R-Ig, which binds to the membrane LT alpha 1 beta 2 heterotrimer, lacked most LN, yet retained a set of mucosal surface draining LN. Since mice genetically deficient in LT alpha lack all LN, including the mucosal set, we hypothesize that a novel LT alpha-dependent pathway controls their genesis. This novel set of mucosal LN cannot be discriminated on the basis of addressin expression. The discovery of LN in mice treated 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 spleen. Our results indicate that both membrane LT alpha beta and soluble LT alpha/TNF mediate T-B cell segregation and the organization of B cell follicles in spleen and LN. Interestingly, while antagonism of membrane LT alpha beta or soluble LT alpha/TNF prevented germinal center (GC) formation in spleen, antagonism of soluble LT alpha/TNF had no effect on LN formation. The data suggest that multiple LT/TNF ligands control B cell follicle organization in the spleen and LN of adult mice, and that the requirements for LT/TNF ligands in GC formation are distinct in the different lymphoid organs.