Abstract
Calcium is a second messenger for many signaling pathways in B cells, but its role as a receptor ligand has not been well characterized. However, pulses of free calcium were found to cause the rapid release of internal calcium stores in normal human B cells. This response appeared to be mediated by a cell surface protein with receptor properties as it could be blocked by pretreatment with trypsin and with kinase and phospholipase Cgamma inhibitors. The calcium receptor on B cells was not the conventional calcium-sensing receptor (CaSR) since B cells did not express CaSR and calcium-induced responses could not be blocked by specific CaSR inhibitors. B-cell responses to extracellular calcium activated phosphoinositide-3 kinase/AKT, calcineurin, extracellular signal regulated kinase, p38 mitogen-activated protein kinase, protein kinase C, Ca(2+)/calmodulin kinase II, and nuclear factor-kappaB signaling pathways, and resulted in transcription of the early response gene, CD83. This extracellular calcium sensor enhanced B-cell responses to Toll-like receptor, B-cell receptor, and cytokine receptor agonists. These findings suggest a means by which B cells prepare to engage in immune responses by responding to calcium fluctuations in their environment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / immunology
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B-Lymphocytes / enzymology
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B-Lymphocytes / immunology*
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CD83 Antigen
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Calcineurin / immunology
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Calcineurin / metabolism
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Calcium / immunology*
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Calcium / metabolism
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Calcium Signaling / immunology*
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Humans
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Immunoglobulins / biosynthesis
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Immunoglobulins / immunology
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / immunology
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NF-kappa B / immunology
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NF-kappa B / metabolism
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Phospholipase C gamma / immunology
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Phospholipase C gamma / metabolism
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Phosphotransferases / immunology
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Phosphotransferases / metabolism
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Receptors, Antigen, B-Cell / immunology
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Receptors, Antigen, B-Cell / metabolism
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Receptors, Calcium-Sensing / antagonists & inhibitors
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Receptors, Calcium-Sensing / immunology
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Receptors, Calcium-Sensing / metabolism
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Receptors, Cytokine / agonists
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Receptors, Cytokine / immunology
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Receptors, Cytokine / metabolism
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Toll-Like Receptors / immunology
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Toll-Like Receptors / metabolism
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Transcription, Genetic / drug effects
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Transcription, Genetic / immunology
Substances
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Antigens, CD
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Immunoglobulins
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Membrane Glycoproteins
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NF-kappa B
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Receptors, Antigen, B-Cell
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Receptors, Calcium-Sensing
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Receptors, Cytokine
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Toll-Like Receptors
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Phosphotransferases
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Calcineurin
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Phospholipase C gamma
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Calcium