Journal
BLOOD
Volume 116, Issue 18, Pages 3456-3464Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-10-249177
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Funding
- Russian Academy of Sciences
- Russian Foundation for Basic Research [09-04-12185]
- Russian Federation [02.120.11.8796]
- Deutsche Forschungsgemeinschaft [SFB633]
- National Institute on Aging, National Institutes of Health
- Helmholtz-Humboldt award
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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. (Blood. 2010;116(18):3456-3464)
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