The Rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands

被引:78
作者
Lin, Kevin B. L. [1 ]
Freeman, Spencer A. [1 ]
Zabetian, Saba [1 ]
Brugger, Hayley [1 ]
Weber, Michele [2 ]
Lei, Victor [1 ]
Dang-Lawson, May [1 ]
Tse, Kathy W. K. [1 ]
Santamaria, Rene [1 ]
Batista, Facundo D. [2 ]
Gold, Michael R. [1 ]
机构
[1] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Inst Life Sci, CELL Res Grp, Vancouver, BC V6T 1Z3, Canada
关键词
D O I
10.1016/j.immuni.2007.11.019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:75 / 87
页数:13
相关论文
共 48 条
[1]   Imaging of germinal center selection events during affinity maturation [J].
Allen, Christopher D. C. ;
Okada, Takaharu ;
Tang, H. Lucy ;
Cyster, Jason G. .
SCIENCE, 2007, 315 (5811) :528-531
[2]   Rap1 promotes cell spreading by localizing Rac guanine nucleoticle exchange factors [J].
Arthur, WT ;
Quilliam, LA ;
Cooper, JA .
JOURNAL OF CELL BIOLOGY, 2004, 167 (01) :111-122
[3]   Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes [J].
Bajenoff, Marc ;
Egen, Jackson G. ;
Koo, Lily Y. ;
Laugier, Jean Pierre ;
Brau, Frederic ;
Glaichenhaus, Nicolas ;
Germain, Ronald N. .
IMMUNITY, 2006, 25 (06) :989-1001
[4]   B cells acquire antigen from target cells after synapse formation [J].
Batista, FD ;
Iber, D ;
Neuberger, MS .
NATURE, 2001, 411 (6836) :489-494
[5]   Cell surface recycling of internalized antigen permits dendritic cell priming of B cells [J].
Bergtold, A ;
Desai, DD ;
Gavhane, A ;
Clyne, R .
IMMUNITY, 2005, 23 (05) :503-514
[6]   Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion [J].
Bivona, TG ;
Wiener, HH ;
Ahearn, IM ;
Silletti, J ;
Chiu, VK ;
Philips, MR .
JOURNAL OF CELL BIOLOGY, 2004, 164 (03) :461-470
[7]   Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation [J].
Bodour, K ;
Zhang, JY ;
Shi, F ;
Leng, S ;
Collins, M ;
Siminovitch, KA .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (01) :99-111
[8]   The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin [J].
Boettner, B ;
Govek, EE ;
Cross, J ;
Van Aelst, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (16) :9064-9069
[9]   Linking Rap to cell adhesion [J].
Bos, JL .
CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (02) :123-128
[10]   B cell recognition of membrane-bound antigen: an exquisite way of sensing ligands [J].
Carrasco, Yolanda R. ;
Batista, Facundo D. .
CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (03) :286-291