The rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands.
B lymphocytes spread and extend membrane processes when searching for antigens and form immune synapses upon contacting cells that display antigens on their surface. Although these dynamic morphological changes facilitate B cell activation, the signaling pathways underlying these processes are not fully understood. We found that activation of the Rap GTPases was essential for these changes in B cell morphology. Rap activation was important for B cell receptor (BCR)- and lymphocyte-function-associated antigen-1 (LFA-1)-induced spreading, for BCR-induced immune-synapse formation, and for particulate BCR ligands to induce localized F-actin assembly and membrane-process extension. Rap activation and F-actin assembly were also required for optimal BCR signaling in response to particulate antigens but not soluble antigens. Thus by controlling B cell morphology and cytoskeletal organization, Rap might play a key role in the activation of B cells by particulate and cell-associated antigens.
Lin
Kevin B L
KB
Department of Microbiology and Immunology, I3 and CELL Research Groups, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Freeman
Spencer A
SA
Zabetian
Saba
S
Brugger
Hayley
H
Weber
Michele
M
Lei
Victor
V
Dang-Lawson
May
M
Tse
Kathy W K
KW
Santamaria
Rene
R
Batista
Facundo D
FD
Gold
Michael R
MR
D000199:Actins / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000648:ultrastructure*; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D020668:rap GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D011947:Receptors, Antigen, B-Cell; D020668:rap GTP-Binding Proteins