Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs.
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.
Tumanov
Alexei V
AV
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow, Russia.
Grivennikov
Sergei I
SI
Kruglov
Andrei A
AA
Shebzukhov
Yuriy V
YV
Koroleva
Ekaterina P
EP
Piao
Yulan
Y
Cui
Chang-Yi
CY
Kuprash
Dmitry V
DV
Nedospasov
Sergei A
SA
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*
D014409:Tumor Necrosis Factor-alpha