Abstract
We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40(+) DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L-huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology*
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CD40 Antigens / genetics
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CD40 Antigens / metabolism
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CD40 Ligand / metabolism
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Cell Communication
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Cell Differentiation
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Cell Movement
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Dendritic Cells / immunology*
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Dinitrophenols / immunology
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Immunization
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Lymphocyte Activation
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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OX40 Ligand
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Ovalbumin / immunology
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Receptors, CXCR5
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Receptors, Chemokine
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Receptors, Cytokine / metabolism
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology*
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Tumor Necrosis Factors
Substances
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CD40 Antigens
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CXCR5 protein, mouse
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Dinitrophenols
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Membrane Glycoproteins
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OX40 Ligand
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Receptors, CXCR5
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Receptors, Chemokine
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Receptors, Cytokine
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Tnfsf4 protein, mouse
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Tumor Necrosis Factors
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dinitrophenol-ovalbumin
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CD40 Ligand
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Ovalbumin