Extracellular calcium sensing promotes human B-cell activation and function.
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.
Hammond
Caitlin M
CM
Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
White
Dionne
D
Tomic
Jelena
J
Shi
Yonghong
Y
Spaner
David E
DE
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D019703:Calcineurin / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D051966:Phospholipase C gamma / Q000276:immunology / Q000378:metabolism; D010770:Phosphotransferases / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D018121:Receptors, Cytokine / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D000097802:CD83 Antigen
D015703:Antigens, CD; D019703:Calcineurin; D002118:Calcium; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D051966:Phospholipase C gamma; D010770:Phosphotransferases; D011947:Receptors, Antigen, B-Cell; D044169:Receptors, Calcium-Sensing; D018121:Receptors, Cytokine; D051193:Toll-Like Receptors; D000097802:CD83 Antigen