Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs

Alexei V. Tumanov, Sergei I. Grivennikov, Andrei A. Kruglov, Yuriy V. Shebzukhov, Ekaterina P. Koroleva, Yulan Piao, Chang Yi Cui, Dmitry V. Kuprash, Sergei A. Nedospasov

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55 Scopus citations

Abstract

Secondary lymphoid organs provide a unique microenvironment for generation of immune responses. Using a cell type-specific conditional knockout approach, we have dissected contributions of tumor necrosis factor (TNF) produced by B cells (B-TNF) or T cells (T-TNF) to the genesis and homeostatic organization of secondary lymphoid organs. In spleen, lymph nodes and Peyer patches, the cellular source of TNF, and its molecular form (soluble versus membrane-bound) appeared distinct. In spleen, in addition to major B-TNF signal, a complementary T-TNF signal contributed to the microstructure. In contrast, B-TNF predominantly controlled the development of follicular dendritic cells and B-cell follicles in Peyer patches. In lymph nodes, cooperation between TNF expressed by B and T cells was necessary for the maintenance of microarchitecture and for generation of an efficient humoral immune response. Unexpectedly, soluble but not membrane TNF expressed by B cells was essential for the organization of the secondary lymphoid organs. Thus, the maintenance of each type of secondary lymphoid organ is orchestrated by distinct contributions of membrane-bound and soluble TNF produced by B and T lymphocytes.

Original languageEnglish (US)
Pages (from-to)3456-3464
Number of pages9
JournalBlood
Volume116
Issue number18
DOIs
StatePublished - Nov 4 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Tumanov, A. V., Grivennikov, S. I., Kruglov, A. A., Shebzukhov, Y. V., Koroleva, E. P., Piao, Y., Cui, C. Y., Kuprash, D. V., & Nedospasov, S. A. (2010). Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs. Blood, 116(18), 3456-3464. https://doi.org/10.1182/blood-2009-10-249177