Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Formation* / genetics
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Apoptosis
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology
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Cell Adhesion Molecules / metabolism
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Chemokine CXCL13
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Chemokines / genetics
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Chemokines / metabolism
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Chemokines, CXC / genetics
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Chemokines, CXC / metabolism
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Dendritic Cells, Follicular / cytology
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Dendritic Cells, Follicular / immunology*
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Dendritic Cells, Follicular / metabolism
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Gene Targeting
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I-kappa B Kinase / genetics
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I-kappa B Kinase / metabolism*
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Immunoglobulin G / immunology
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Lymphoid Tissue / cytology
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Lymphoid Tissue / metabolism
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Mice
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Mice, Transgenic
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Receptors, Complement 3d / genetics
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Receptors, Tumor Necrosis Factor, Type I / genetics
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Receptors, Tumor Necrosis Factor, Type I / metabolism*
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Transcription Factors / metabolism
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Up-Regulation
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Cell Adhesion Molecules
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Chemokine CXCL13
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Chemokines
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Chemokines, CXC
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Cxcl13 protein, mouse
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Immunoglobulin G
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Receptors, Complement 3d
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Receptors, Tumor Necrosis Factor, Type I
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Transcription Factors
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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I-kappa B Kinase
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Ikbkb protein, mouse