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

Blood. 2010 Nov 4;116(18):3456-64. doi: 10.1182/blood-2009-10-249177. Epub 2010 Jul 15.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Gene Expression Regulation
  • Immunity, Humoral
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Lymph Nodes / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peyer's Patches / cytology
  • Peyer's Patches / immunology*
  • Spleen / cytology
  • Spleen / immunology*
  • Spleen / ultrastructure
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*


  • Tumor Necrosis Factor-alpha