Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs

P D Rennert, J L Browning, R Mebius, F Mackay, P S Hochman

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For more than a decade, the biological roles and the apparent redundancy of the cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) have been debated. LT alpha exists in its soluble form as a homotrimer, which like TNF only binds the TNF receptors, TNF-R55 or TNF-R75. The cell surface form of LT exists as a heteromer of LT alpha and LT beta subunits and this complex specifically binds the LT beta receptor (LT beta-R). To discriminate the functions of the LT and TNF systems, soluble LT beta-R-immunoglobulin (Ig) or TNF-R-Ig fusion proteins were introduced into embryonic circulation by injecting pregnant mice. Exposure to LT beta-R-Ig during gestation disrupted lymph node development and splenic architecture in the progeny indicating that both effects are mediated by the surface LT alpha/beta complex. These data are the first to identify a cell surface ligand involved in immune organ morphogenesis. Moreover, they unambiguously discriminate the functions of the various TNF/LT ligands, provide a unique model to study compartmentalization of immune responses and illustrate the generic utility of receptor-Ig fusion proteins for dissecting/ordering ontogenetic events in the absence of genetic modifications.

Original languageEnglish
Pages (from-to)1999-2006
Number of pages8
JournalJournal of Experimental Medicine
Issue number5
Publication statusPublished - 1 Nov 1996


  • Animals
  • Cell Membrane/metabolism
  • Immunoglobulin G/pharmacology
  • Lymph Nodes/embryology
  • Lymphoid Tissue/embryology
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha/metabolism
  • Membrane Proteins/metabolism
  • Mice
  • Mice, Inbred BALB C
  • Morphogenesis
  • Peyer's Patches/embryology
  • Receptors, Tumor Necrosis Factor/immunology
  • Recombinant Fusion Proteins/pharmacology
  • Spleen/embryology
  • Tumor Necrosis Factor-alpha/metabolism

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