Role of initial protein phosphorylation events and localized release-activated calcium influx in B cell antigen receptor signaling.
An increase in intracellular calcium concentration is one of the major initial steps in B cell activation following antigen receptor (BCR) ligation. We show herein that in C57BL/6 murine B lymphocytes and in model cell lines, BCR-mediated calcium ion (Ca(2+)) influx occurs via highly selective Ca(2+) release-activated channels, and stromal interaction molecule 1 (STIM1) plays an important role in this pathway. We also demonstrate the temporal relation between Ca(2+)-dependent signaling events and formation of the immune synapse. Our data indicate that cytoplasmic Ca(2+) levels in areas adjacent to the immune synapse differ from those in the rest of the cytoplasm. Finally, a comparison of phosphorylation patterns of BCR-triggered signaling proteins in the presence or absence of Ca(2+) revealed the unanticipated finding that initial BCR-triggered, Ca(2+)-dependent tyrosine phosphorylation events involve predominantly Ca(2+) released from intracellular stores and that influx-derived Ca(2+) is not essential. This suggests a different role for this phase of Ca(2+) influx.
Lyubchenko
Taras
T
Department of Medicine and Immunology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA. taras.lyubchenko@uchsc.edu
Nielsen
J Paul
JP
Miller
Sara M
SM
Liubchenko
Ganna A
GA
Holers
V Michael
VM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D020013:Calcium Signaling / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D003470:Culture Media; D003593:Cytoplasm / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D054992:Immunological Synapses / Q000276:immunology; D042541:Intracellular Space / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D017136:Ion Transport; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D000071737:Stromal Interaction Molecule 1
D015220:Calcium Channels; D003470:Culture Media; D007473:Ion Channels; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D019000:Phosphotyrosine; D002118:Calcium