Abstract
Notch2 and B cell antigen receptor (BCR) signaling determine whether transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it is unknown how these pathways are related. We generated Taok3-/- mice, lacking the serine/threonine kinase Taok3, and found cell-intrinsic defects in the development of MZB but not FoB cells. Type 1 transitional (T1) B cells required Taok3 to rapidly respond to ligation by the Notch ligand Delta-like 1. BCR ligation by endogenous or exogenous ligands induced the surface expression of the metalloproteinase ADAM10 on T1 B cells in a Taok3-dependent manner. T1 B cells expressing surface ADAM10 were committed to becoming MZB cells in vivo, whereas T1 B cells lacking expression of ADAM10 were not. Thus, during positive selection in the spleen, BCR signaling causes immature T1 B cells to become receptive to Notch ligands via Taok3-mediated surface expression of ADAM10.
MeSH terms
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ADAM10 Protein / genetics
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ADAM10 Protein / metabolism*
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Adaptive Immunity*
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Amyloid Precursor Protein Secretases / genetics
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Amyloid Precursor Protein Secretases / metabolism*
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Animals
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B-Lymphocytes / physiology*
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Cell Differentiation*
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Cell Lineage*
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Cells, Cultured
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Clonal Selection, Antigen-Mediated
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Gene Expression Regulation
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Germinal Center / immunology*
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Receptor, Notch2 / metabolism
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Receptors, Antigen, B-Cell / metabolism
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Signal Transduction
Substances
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Dll3 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Notch2 protein, mouse
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Receptor, Notch2
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Receptors, Antigen, B-Cell
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Protein Serine-Threonine Kinases
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Tack3 kinase, mouse
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Amyloid Precursor Protein Secretases
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ADAM10 Protein
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Adam10 protein, mouse