Abstract
We demonstrated that B-cell-dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8(+) T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell-deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyS(high) peptide-pulsed bone marrow-derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell-deficient and TACI-deficient mice, strongly supporting a need for B-cell-DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Apoptosis
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B-Lymphocytes / metabolism*
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B7-2 Antigen / metabolism
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Bone Marrow / immunology
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Bone Marrow / metabolism
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CD40 Antigens / genetics
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CD40 Antigens / physiology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cytotoxicity, Immunologic
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Female
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Immunization
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Interleukin-2 / genetics
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Interleukin-2 / physiology
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Interleukin-4 / genetics
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Interleukin-4 / physiology
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Lymphocyte Activation / immunology*
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Male
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology*
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Recombinant Fusion Proteins / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Transmembrane Activator and CAML Interactor Protein
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Vaccination
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beta 2-Microglobulin / genetics
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beta 2-Microglobulin / physiology
Substances
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B7-2 Antigen
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CD40 Antigens
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Interleukin-2
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Membrane Proteins
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Peptide Fragments
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Receptors, Tumor Necrosis Factor
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Recombinant Fusion Proteins
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Tnfrsf13b protein, mouse
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Transmembrane Activator and CAML Interactor Protein
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beta 2-Microglobulin
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Interleukin-4