FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses

Immunity. 2006 Jan;24(1):65-77. doi: 10.1016/j.immuni.2005.11.013.


The FDC-specific molecular signals required in the formation of FDC networks, B cell follicles, and germinal centers (GCs) have remained poorly understood. We used FDC-specific gene targeting to investigate the function of p55TNFR and IKK2 in lymphoid organ structure and function. Here we show that FDC-specific expression of p55TNFR is necessary and sufficient to promote FDC network and B cell follicle formation, restore the expression of CXCL13 and VCAM-1/ICAM-1 in FDCs, and lead to productive GCs. Notably, FDC-specific disruption of IKK2 does not affect formation of FDC networks. Yet, after antigen engagement or immune complex (IC) deposition, FDCs lacking IKK2 fail to upregulate VCAM-1 and ICAM-1, and GCs remain sterile. These findings demonstrate that IKK2-independent function of p55TNFR on FDCs is sufficient to support the development of FDC networks and GCs, while FDC-specific IKK2 is indispensable for the generation of efficient humoral immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation* / genetics
  • Apoptosis
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cell Adhesion Molecules / metabolism
  • Chemokine CXCL13
  • Chemokines / genetics
  • Chemokines / metabolism
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism
  • Dendritic Cells, Follicular / cytology
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Gene Targeting
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Immunoglobulin G / immunology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / metabolism
  • Mice
  • Mice, Transgenic
  • Receptors, Complement 3d / genetics
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Receptors, Tumor Necrosis Factor, Type I / metabolism*
  • Transcription Factors / metabolism
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Cell Adhesion Molecules
  • Chemokine CXCL13
  • Chemokines
  • Chemokines, CXC
  • Cxcl13 protein, mouse
  • Immunoglobulin G
  • Receptors, Complement 3d
  • Receptors, Tumor Necrosis Factor, Type I
  • Transcription Factors
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • I-kappa B Kinase
  • Ikbkb protein, mouse