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 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.
Rennert
P D
PD
Department of Immunology/Inflammation, Biogen Inc., Cambridge, MA 02142, USA.
Browning
J L
JL
Hochman
P S
PS
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology; D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology; D018968:CD58 Antigens / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D053308:Lymphotoxin-beta; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000196:embryology; D011247:Pregnancy; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D013601:T-Lymphocytes / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D015703:Antigens, CD; D000954:Antigens, Surface; D018968:CD58 Antigens; C069886:L-selectin counter-receptors; C505886:LTB protein, human; D008024:Ligands; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha