title: TNF and lymphotoxin beta cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes.
abstract: Inactivation of genes encoding members of TNF and TNF receptor families reveal their divergent roles in the formation and function of secondary lymphoid organs. Most lymphotoxin alpha (ltalpha)- and all lymphotoxin beta receptor (ltbetar)-deficient mice are completely devoid of lymph nodes (LNs); however, most lymphotoxin beta (ltbeta)-deficient mice develop mesenteric LNs. Tnf- and tnfrp55-deficient mice develop a complete set of LNs, while ltbeta/tnfrp55 double-deficient mice lack all LNs, demonstrating cooperation between LTbeta and TNFRp55 in LN development. Now we report that ltbeta/tnf double-deficient mice develop the same set of mucosal LNs as do ltbeta-deficient mice, suggesting that ligands other than TNF signal through TNFRp55 during LN development. These LNs retain distinct T and B cells areas; however, they lack follicular dendritic cell networks. Structures resembling germinal centers can be found in the LNs from immunized ltbeta-deficient mice but not in ltbeta/tnf double-deficient mice. Additionally, stromal components of the spleen and LNs appear to be more severely disturbed in ltbeta/tnf double-deficient mice as compared with ltbeta-deficient mice. We conclude that LTbeta and TNF cooperate in the establishment of the correct microarchitecture of lymphoid organs.
authors.affiliation: Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow State University, Russia. kupras@imb.ac.ru
authors.forename: D V
authors.initials: DV
authors.lastname: Kuprash
authors.forename: M B
authors.initials: MB
authors.lastname: Alimzhanov
authors.forename: A V
authors.initials: AV
authors.lastname: Tumanov
authors.forename: A O
authors.initials: AO
authors.lastname: Anderson
authors.forename: K
authors.initials: K
authors.lastname: Pfeffer
authors.forename: S A
authors.initials: SA
authors.lastname: Nedospasov
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004357:Drug Synergism; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology* / Q000196:embryology* / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology* / Q000196:embryology* / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology*; D053308:Lymphotoxin-beta; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000196:embryology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha