Abstract
The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies / immunology
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Antibody Formation / immunology
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B-Cell Activating Factor / chemistry
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B-Cell Activating Factor / genetics
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B-Cell Activating Factor / metabolism*
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B-Cell Activation Factor Receptor / immunology
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B-Cell Activation Factor Receptor / metabolism
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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Cell Line
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Cell Proliferation
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Histocompatibility Antigens Class II / immunology
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Humans
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Immunoglobulins / biosynthesis
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Immunoglobulins / immunology
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Ligands
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Lymphocyte Activation*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Sequence Alignment
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Signal Transduction
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Spleen / immunology
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Transmembrane Activator and CAML Interactor Protein / deficiency
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Transmembrane Activator and CAML Interactor Protein / genetics
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Transmembrane Activator and CAML Interactor Protein / metabolism*
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Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
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Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism*
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Up-Regulation
Substances
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Antibodies
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B-Cell Activating Factor
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B-Cell Activation Factor Receptor
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Histocompatibility Antigens Class II
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Immunoglobulins
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Ligands
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TNFSF13B protein, human
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Tnfrsf13b protein, mouse
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Tnfsf13b protein, mouse
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Transmembrane Activator and CAML Interactor Protein
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Tumor Necrosis Factor Ligand Superfamily Member 13