title: Distinct calcium channels regulate responses of primary B lymphocytes to B cell receptor engagement and mechanical stimuli.
abstract: Intracellular Ca(2+) plays a central role in controlling lymphocyte function. Nonetheless, critical gaps remain in our understanding of the mechanisms that regulate its concentration. Although Ca(2+)-release-activated calcium (CRAC) channels are the primary Ca(2+) entry pathways in T cells, additional pathways appear to be operative in B cells. Our efforts to delineate these pathways in primary murine B cells reveal that Ca(2+)-permeant nonselective cation channels (NSCCs) operate in a cooperative fashion with CRAC. Interestingly, these non-CRAC channels are selectively activated by mechanical stress, although the mechanism overlaps with BCR-activated pathways, suggesting that they may operate in concert to produce functionally diverse Ca(2+) signals. NSCCs also regulate the membrane potential, which activates integrin-dependent binding of B cells to extracellular matrix elements involved in their trafficking and localization within secondary lymphoid organs. Thus, CRAC and distinct Ca(2+) permeant NSCCs are differentially activated by the BCR and mechanical stimuli and regulate distinct aspects of B cell physiology.
authors.affiliation: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Wen
authors.forename: Brian
authors.initials: B
authors.lastname: Hondowicz
authors.forename: Leslie
authors.initials: L
authors.lastname: King
authors.forename: John
authors.initials: J
authors.lastname: Monroe
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Freedman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015153:Blotting, Western; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018408:Patch-Clamp Techniques; D051966:Phospholipase C gamma; D010812:Physical Stimulation; D016133:Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D010738:Type C Phospholipases / Q000276:immunology / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D016023:Integrins; D011947:Receptors, Antigen, B-Cell; D010738:Type C Phospholipases; D051966:Phospholipase C gamma