title: Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs.
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.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow, Russia.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tumanov
authors.forename: Sergei I
authors.initials: SI
authors.lastname: Grivennikov
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Kruglov
authors.forename: Yuriy V
authors.initials: YV
authors.lastname: Shebzukhov
authors.forename: Ekaterina P
authors.initials: EP
authors.lastname: Koroleva
authors.forename: Yulan
authors.initials: Y
authors.lastname: Piao
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Cui
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kuprash
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation; D056724:Immunity, Humoral; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha