TNF receptor-1 is required for the formation of splenic compartments during adult, but not embryonic life

Novica M. Milićević, Karola Klaperski, Klaus Nohroudi, Živana Milićević, Katja Bieber, Babett Baraniec, Maike Blessenohl, Kathrin Kalies, Carl F. Ware, Jürgen Westermann*

*Corresponding author for this work
14 Citations (Scopus)


Lymphotoxin β-receptor (LTβR) and TNF receptor-1 (TNFR1) are important for the development of secondary lymphoid organs during embryonic life. The significance of LTβR and TNFR1 for the formation of lymphoid tissue during adult life is not well understood. Immunohistochemistry, morphometry, flow cytometry, and laser microdissection were used to compare wild-type, LTβR-/-, TNFR1-/- spleens with splenic tissue that has been newly formed 8 wk after avascular implantation into adult mice. During ontogeny, LTβR is sufficient to induce formation of the marginal zone, similar-sized T and B cell zones, and a mixed T/B cell zone that completely surrounded the T cell zone. Strikingly, in adult mice, the formation of splenic compartments required both LTβR and TNFR1 expression, demonstrating that the molecular requirements for lymphoid tissue formation are different during embryonic and adult life. Thus, interfering with the TNFR1 pathway offers the possibility to selectively block the formation of ectopic lymphoid tissue and at the same time to spare secondary lymphoid organs such as spleen and lymph nodes. This opens a new perspective for the treatment of autoimmune and inflammatory diseases.

Original languageEnglish
JournalJournal of Immunology
Issue number3
Pages (from-to)1486-1494
Number of pages9
Publication statusPublished - 01.02.2011

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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