Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
B Cell Ligand Discrimination Through a Spreading and Contraction Response
S. J. Fleire,1J. P. Goldman,2,3Y. R. Carrasco,1M. Weber,1D. Bray,3F. D. Batista1*
B cells recognize foreign antigens by virtue of cell surfaceimmunoglobulin receptors and are most effectively activatedby membrane-bound ligands. Here, we show that in the early stagesof this process, B cells exhibit a two-phase response in whichthey first spread over the antigen-bearing membrane and thencontract, thereby collecting bound antigen into a central aggregate.The extent of this response, which is both signaling- and actin-dependent,determines the quantity of antigen accumulated and hence thedegree of B cell activation. Brownian dynamic simulations reproduceessential features of the antigen collection process and suggesta possible basis for affinity discrimination. We propose thatdynamic spreading is an important step of the immune response.
1 Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. 2 Computing Laboratory, University of Kent, Canterbury CT2 7NF, UK. 3 Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
* To whom correspondence should be addressed. E-mail: facundo.batista{at}cancer.org.uk
B Cell Receptor-induced Phosphorylation of Pyk2 and Focal Adhesion Kinase Involves Integrins and the Rap GTPases and Is Required for B Cell Spreading.
K. W. K. Tse, M. Dang-Lawson, R. L. Lee, D. Vong, A. Bulic, L. Buckbinder, and M. R. Gold (2009)
J. Biol. Chem.
284, 22865-22877
|Abstract »|Full Text »|PDF »
Down-regulation of CXCR4 and CD62L in Chronic Lymphocytic Leukemia Cells Is Triggered by B-Cell Receptor Ligation and Associated with Progressive Disease.
A. Vlad, P.-A. Deglesne, R. Letestu, S. Saint-Georges, N. Chevallier, F. Baran-Marszak, N. Varin-Blank, F. Ajchenbaum-Cymbalista, and D. Ledoux (2009)
Cancer Res.
69, 6387-6395
|Abstract »|Full Text »|PDF »
Visualizing B cell capture of cognate antigen from follicular dendritic cells.
K. Suzuki, I. Grigorova, T. G. Phan, L. M. Kelly, and J. G. Cyster (2009)
J. Exp. Med.
206, 1485-1493
|Abstract »|Full Text »|PDF »
BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation.
D. Depoil, M. Weber, B. Treanor, S. J. Fleire, Y. R. Carrasco, N. E. Harwood, and F. D. Batista (2009)
Science Signaling
2, pt1
|Abstract »|Full Text »|PDF »
Integrins in immunity.
R. Evans, I. Patzak, L. Svensson, K. De Filippo, K. Jones, A. McDowall, and N. Hogg (2009)
J. Cell Sci.
122, 215-225
|Abstract »|Full Text »|PDF »
Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis.
A. Meyer-Bahlburg, S. Becker-Herman, S. Humblet-Baron, S. Khim, M. Weber, G. Bouma, A. J. Thrasher, F. D. Batista, and D. J. Rawlings (2008)
Blood
112, 4158-4169
|Abstract »|Full Text »|PDF »
Facundo Batista: watching B cells spread and grab antigens.
H. Bashyam (2008)
J. Exp. Med.
205, 1718-1719
|Full Text »|PDF »
Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells.
S. H. Wimmer-Kleikamp, E. Nievergall, K. Gegenbauer, S. Adikari, M. Mansour, T. Yeadon, A. W. Boyd, N. R. Patani, and M. Lackmann (2008)
Blood
112, 721-732
|Abstract »|Full Text »|PDF »
Membrane heterogeneities in the formation of B cell receptor-Lyn kinase microclusters and the immune synapse.
Regulation of integrin activation through the B-cell receptor.
E. Arana, N. E. Harwood, and F. D. Batista (2008)
J. Cell Sci.
121, 2279-2286
|Abstract »|Full Text »|PDF »
Transfusion of IgG-Opsonized Foreign Red Blood Cells Mediates Reduction of Antigen-Specific B Cell Priming in a Murine Model.
D. Brinc, H. Le-Tien, A. R. Crow, V. Siragam, J. Freedman, and A. H. Lazarus (2008)
J. Immunol.
181, 948-953
|Abstract »|Full Text »|PDF »
B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo.
P. Barral, J. Eckl-Dorna, N. E. Harwood, C. De Santo, M. Salio, P. Illarionov, G. S. Besra, V. Cerundolo, and F. D. Batista (2008)
PNAS
105, 8345-8350
|Abstract »|Full Text »|PDF »
Capture of plasma membrane fragments from target cells by trogocytosis requires signaling in T cells but not in B cells.
A. Aucher, E. Magdeleine, E. Joly, and D. Hudrisier (2008)
Blood
111, 5621-5628
|Abstract »|Full Text »|PDF »
Phospholipase C-{gamma}2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen.
M. Weber, B. Treanor, D. Depoil, H. Shinohara, N. E. Harwood, M. Hikida, T. Kurosaki, and F. D. Batista (2008)
J. Exp. Med.
205, 853-868
|Abstract »|Full Text »|PDF »
Dendritic Cell-Dependent Inhibition of B Cell Proliferation Requires CD22.
L. Santos, K. E. Draves, M. Boton, P. K. Grewal, J. D. Marth, and E. A. Clark (2008)
J. Immunol.
180, 4561-4569
|Abstract »|Full Text »|PDF »
Live Cell Imaging Reveals that the Inhibitory Fc{gamma}RIIB Destabilizes B Cell Receptor Membrane-Lipid Interactions and Blocks Immune Synapse Formation.
B Cell Antigen Receptor-Induced Rac1 Activation and Rac1-Dependent Spreading Are Impaired in Transitional Immature B Cells Due to Levels of Membrane Cholesterol.
Syk-dependent Actin Dynamics Regulate Endocytic Trafficking and Processing of Antigens Internalized through the B-Cell Receptor.
D. Le Roux, D. Lankar, M.-I. Yuseff, F. Vascotto, T. Yokozeki, G. Faure-Andre, E. Mougneau, N. Glaichenhaus, B. Manoury, C. Bonnerot, et al. (2007)
Mol. Biol. Cell
18, 3451-3462
|Abstract »|Full Text »|PDF »
The actin-based motor protein myosin II regulates MHC class II trafficking and BCR-driven antigen presentation.
F. Vascotto, D. Lankar, G. Faure-Andre, P. Vargas, J. Diaz, D. Le Roux, M.-I. Yuseff, J.-B. Sibarita, M. Boes, G. Raposo, et al. (2007)
J. Cell Biol.
176, 1007-1019
|Abstract »|Full Text »|PDF »
Phylogenetic Divergence of CD47 Interactions with Human Signal Regulatory Protein {alpha} Reveals Locus of Species Specificity: IMPLICATIONS FOR THE BINDING SITE.
S. Subramanian, E. T. Boder, and D. E. Discher (2007)
J. Biol. Chem.
282, 1805-1818
|Abstract »|Full Text »|PDF »
Segregation of HLA-C from ICAM-1 at NK Cell Immune Synapses Is Controlled by Its Cell Surface Density.