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

Blood, ISSN: 0006-4971, Vol: 116, Issue: 18, Page: 3456-3464
2010
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Article Description

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.

Bibliographic Details

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

American Society of Hematology

Biochemistry, Genetics and Molecular Biology; Immunology and Microbiology; Medicine

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