B cell receptor-induced Ca2+ mobilization mediates F-actin rearrangements and is indispensable for adhesion and spreading of B lymphocytes.
B cells acquire membrane-bound cognate antigens from the surface of the APCs by forming an IS, similar to that seen in T cells. Recognition of membrane-bound antigens on the APCs initiates adhesion of B lymphocytes to the antigen-tethered surface, which is followed by the formation of radial lamellipodia-like structures, a process known as B cell spreading. The spreading response requires the rearrangement of the submembrane actin cytoskeleton and is regulated mainly via signals transmitted by the BCR. Here, we show that cytoplasmic calcium is a regulator of actin cytoskeleton dynamics in B lymphocytes. We find that BCR-induced calcium mobilization is indispensible for adhesion and spreading of B cells and that PLCγ and CRAC-mediated calcium mobilization are critical regulators of these processes. Measuring calcium and actin dynamics in live cells, we found that a generation of actin-based membrane protrusion is strongly linked to the dynamics of a cytoplasmic-free calcium level. Finally, we demonstrate that PLCγ and CRAC channels regulate the activity of actin-severing protein cofilin, linking BCR-induced calcium signaling to the actin dynamics.
Eötvös Lóránd University, Pázmány Péter sétány 1/c, Budapest, Hungary.
Máté
M
Maus
David
D
Medgyesi
Endre
E
Kiss
Andrea E
AE
Schneider
Agnes
A
Enyedi
Nóra
N
Szilágyi
János
J
Matkó
Gabriella
G
Sármay
D008841:Actin Cytoskeleton / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D051338:Cofilin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D051966:Phospholipase C gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011554:Pseudopodia / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014161:Transduction, Genetic
D000199:Actins; D015220:Calcium Channels; C495811:Cfl1 protein, mouse; D051338:Cofilin 1; D011947:Receptors, Antigen, B-Cell; D051966:Phospholipase C gamma; D002118:Calcium