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.


Logo for

Science 312 (5774): 738-741

Copyright © 2006 by the American Association for the Advancement of Science

B Cell Ligand Discrimination Through a Spreading and Contraction Response

S. J. Fleire,1 J. P. Goldman,2,3 Y. R. Carrasco,1 M. Weber,1 D. Bray,3 F. D. Batista1*

Abstract: B cells recognize foreign antigens by virtue of cell surface immunoglobulin receptors and are most effectively activated by membrane-bound ligands. Here, we show that in the early stages of this process, B cells exhibit a two-phase response in which they first spread over the antigen-bearing membrane and then contract, 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 the degree of B cell activation. Brownian dynamic simulations reproduce essential features of the antigen collection process and suggest a possible basis for affinity discrimination. We propose that dynamic 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}

Mutations of Cx43 that affect B cell spreading in response to BCR signaling.
L. Falk, M. Dang-Lawson, J. L. Vega, F. Pournia, K. Choi, C. Jang, C. C. Naus, and L. Matsuuchi (2014)
Biology Open 3, 185-194
   Abstract »    Full Text »    PDF »
Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells.
A. M. Avalos, A. M. Bilate, M. D. Witte, A. K. Tai, J. He, M. P. Frushicheva, P. D. Thill, F. Meyer-Wentrup, C. S. Theile, A. K. Chakraborty, et al. (2014)
J. Exp. Med. 211, 365-379
   Abstract »    Full Text »    PDF »
T Lymphocytes Sense Antigens within Seconds and Make a Decision within One Minute.
A. Brodovitch, P. Bongrand, and A. Pierres (2013)
J. Immunol. 191, 2064-2071
   Abstract »    Full Text »    PDF »
Vinculin Arrests Motile B Cells by Stabilizing Integrin Clustering at the Immune Synapse.
J. Saez de Guinoa, L. Barrio, and Y. R. Carrasco (2013)
J. Immunol. 191, 2742-2751
   Abstract »    Full Text »    PDF »
IL-4 Upregulates Ig{alpha} and Ig{beta} Protein, Resulting in Augmented IgM Maturation and B Cell Receptor-Triggered B Cell Activation.
B. Guo and T. L. Rothstein (2013)
J. Immunol. 191, 670-677
   Abstract »    Full Text »    PDF »
B Cells Use Mechanical Energy to Discriminate Antigen Affinities.
E. Natkanski, W.-Y. Lee, B. Mistry, A. Casal, J. E. Molloy, and P. Tolar (2013)
Science 340, 1587-1590
   Abstract »    Full Text »    PDF »
B Cell Activation Is Regulated by the Stiffness Properties of the Substrate Presenting the Antigens.
Z. Wan, S. Zhang, Y. Fan, K. Liu, F. Du, A. M. Davey, H. Zhang, W. Han, C. Xiong, and W. Liu (2013)
J. Immunol. 190, 4661-4675
   Abstract »    Full Text »    PDF »
B cell receptor-induced Ca2+ mobilization mediates F-actin rearrangements and is indispensable for adhesion and spreading of B lymphocytes.
M. Maus, D. Medgyesi, E. Kiss, A. E. Schneider, A. Enyedi, N. Szilagyi, J. Matko, and G. Sarmay (2013)
J. Leukoc. Biol. 93, 537-547
   Abstract »    Full Text »    PDF »
Germinal center B cells govern their own fate via antibody feedback.
Y. Zhang, M. Meyer-Hermann, L. A. George, M. T. Figge, M. Khan, M. Goodall, S. P. Young, A. Reynolds, F. Falciani, A. Waisman, et al. (2013)
J. Exp. Med. 210, 457-464
   Abstract »    Full Text »    PDF »
The Dok-3/Grb2 Protein Signal Module Attenuates Lyn Kinase-dependent Activation of Syk Kinase in B Cell Antigen Receptor Microclusters.
M. Losing, I. Goldbeck, B. Manno, T. Oellerich, T. Schnyder, H. Bohnenberger, B. Stork, H. Urlaub, F. D. Batista, J. Wienands, et al. (2013)
J. Biol. Chem. 288, 2303-2313
   Abstract »    Full Text »    PDF »
Monovalent and Multivalent Ligation of the B Cell Receptor Exhibit Differential Dependence upon Syk and Src Family Kinases.
S. Mukherjee, J. Zhu, J. Zikherman, R. Parameswaran, T. A. Kadlecek, Q. Wang, B. Au-Yeung, H. Ploegh, J. Kuriyan, J. Das, et al. (2013)
Science Signaling 6, ra1
   Abstract »    Full Text »    PDF »
Macrophages induce differentiation of plasma cells through CXCL10/IP-10.
W. Xu, H. Joo, S. Clayton, M. Dullaers, M.-C. Herve, D. Blankenship, M. T. De La Morena, R. Balderas, C. Picard, J.-L. Casanova, et al. (2012)
J. Exp. Med. 209, 1813-1823
   Abstract »    Full Text »    PDF »
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.
T. Yokosuka, M. Takamatsu, W. Kobayashi-Imanishi, A. Hashimoto-Tane, M. Azuma, and T. Saito (2012)
J. Exp. Med. 209, 1201-1217
   Abstract »    Full Text »    PDF »
Marginal Zone B Cells Regulate Antigen-Specific T Cell Responses during Infection.
R. Bankoti, K. Gupta, A. Levchenko, and S. Stager (2012)
J. Immunol. 188, 3961-3971
   Abstract »    Full Text »    PDF »
Actin Reorganization Is Required for the Formation of Polarized B Cell Receptor Signalosomes in Response to Both Soluble and Membrane-Associated Antigens.
C. Liu, H. Miller, G. Orlowski, H. Hang, A. Upadhyaya, and W. Song (2012)
J. Immunol. 188, 3237-3246
   Abstract »    Full Text »    PDF »
Intrinsic Differences in the Initiation of B Cell Receptor Signaling Favor Responses of Human IgG+ Memory B Cells over IgM+ Naive B Cells.
A. M. Davey and S. K. Pierce (2012)
J. Immunol. 188, 3332-3341
   Abstract »    Full Text »    PDF »
Cofilin-Mediated F-Actin Severing Is Regulated by the Rap GTPase and Controls the Cytoskeletal Dynamics That Drive Lymphocyte Spreading and BCR Microcluster Formation.
S. A. Freeman, V. Lei, M. Dang-Lawson, K. Mizuno, C. D. Roskelley, and M. R. Gold (2011)
J. Immunol. 187, 5887-5900
   Abstract »    Full Text »    PDF »
Myosin 1c Participates in B Cell Cytoskeleton Rearrangements, Is Recruited to the Immunologic Synapse, and Contributes to Antigen Presentation.
J. L. Maravillas-Montero, P. G. Gillespie, G. Patino-Lopez, S. Shaw, and L. Santos-Argumedo (2011)
J. Immunol. 187, 3053-3063
   Abstract »    Full Text »    PDF »
The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85.
T. Oellerich, V. Bremes, K. Neumann, H. Bohnenberger, K. Dittmann, H.-H. Hsiao, M. Engelke, T. Schnyder, F. D. Batista, H. Urlaub, et al. (2011)
EMBO J. 30, 3620-3634
   Abstract »    Full Text »    PDF »
CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics.
J. Saez de Guinoa, L. Barrio, M. Mellado, and Y. R. Carrasco (2011)
Blood 118, 1560-1569
   Abstract »    Full Text »    PDF »
The gap junction protein Cx43 regulates B-lymphocyte spreading and adhesion.
S. Machtaler, M. Dang-Lawson, K. Choi, C. Jang, C. C. Naus, and L. Matsuuchi (2011)
J. Cell Sci. 124, 2611-2621
   Abstract »    Full Text »    PDF »
A Balance of Bruton's Tyrosine Kinase and SHIP Activation Regulates B Cell Receptor Cluster Formation by Controlling Actin Remodeling.
C. Liu, H. Miller, K. L. Hui, B. Grooman, S. Bolland, A. Upadhyaya, and W. Song (2011)
J. Immunol. 187, 230-239
   Abstract »    Full Text »    PDF »
Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity.
B. Treanor, D. Depoil, A. Bruckbauer, and F. D. Batista (2011)
J. Exp. Med. 208, 1055-1068
   Abstract »    Full Text »    PDF »
Immunoinhibitory Adapter Protein Src Homology Domain 3 Lymphocyte Protein 2 (SLy2) Regulates Actin Dynamics and B Cell Spreading.
M. von Holleben, A. Gohla, K.-P. Janssen, B. M. Iritani, and S. Beer-Hammer (2011)
J. Biol. Chem. 286, 13489-13501
   Abstract »    Full Text »    PDF »
The Cytoskeleton Coordinates the Early Events of B-cell Activation.
N. E. Harwood and F. D. Batista (2011)
Cold Spring Harb Perspect Biol 3, a002360
   Abstract »    Full Text »    PDF »
Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleen.
E. Manevich-Mendelson, V. Grabovsky, S. W. Feigelson, G. Cinamon, Y. Gore, G. Goverse, S. J. Monkley, R. Margalit, D. Melamed, R. E. Mebius, et al. (2010)
Blood 116, 5907-5918
   Abstract »    Full Text »    PDF »
It's All About Change: The Antigen-driven Initiation of B-Cell Receptor Signaling.
W. Liu, H. W. Sohn, P. Tolar, and S. K. Pierce (2010)
Cold Spring Harb Perspect Biol 2, a002295
   Abstract »    Full Text »    PDF »
Bam32/DAPP1 Promotes B Cell Adhesion and Formation of Polarized Conjugates with T Cells.
M. Al-Alwan, S. Hou, T.-t. Zhang, K. Makondo, and A. J. Marshall (2010)
J. Immunol. 184, 6961-6969
   Abstract »    Full Text »    PDF »
Affinity measured by microcluster.
D. R. Fooksman and M. L. Dustin (2010)
J. Exp. Med. 207, 907-909
   Abstract »    Full Text »    PDF »
Antigen affinity discrimination is an intrinsic function of the B cell receptor.
W. Liu, T. Meckel, P. Tolar, H. W. Sohn, and S. K. Pierce (2010)
J. Exp. Med. 207, 1095-1111
   Abstract »    Full Text »    PDF »
Antigen-Induced Oligomerization of the B Cell Receptor Is an Early Target of Fc{gamma}RIIB Inhibition.
W. Liu, H. Won Sohn, P. Tolar, T. Meckel, and S. K. Pierce (2010)
J. Immunol. 184, 1977-1989
   Abstract »    Full Text »    PDF »
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.
J. Eckl-Dorna and F. D. Batista (2009)
Blood 113, 3969-3977
   Abstract »    Full Text »    PDF »
Early Events of B Cell Activation by Antigen.
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 »
Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn.
D. Brinc and A. H. Lazarus (2009)
Hematology 2009, 185-191
   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.
H. W. Sohn, P. Tolar, and S. K. Pierce (2008)
J. Cell Biol. 182, 367-379
   Abstract »    Full Text »    PDF »
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.
H. W. Sohn, S. K. Pierce, and S.-J. Tzeng (2008)
J. Immunol. 180, 793-799
   Abstract »    Full Text »    PDF »
B Cell Antigen Receptor-Induced Rac1 Activation and Rac1-Dependent Spreading Are Impaired in Transitional Immature B Cells Due to Levels of Membrane Cholesterol.
R. J. Brezski and J. G. Monroe (2007)
J. Immunol. 179, 4464-4472
   Abstract »    Full Text »    PDF »
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.
C. R. Almeida and D. M. Davis (2006)
J. Immunol. 177, 6904-6910
   Abstract »    Full Text »    PDF »
B cells spread to affinity.
A. Katsnelson (2006)
J. Cell Biol. 173, 642
   Full Text »    PDF »
IMMUNOLOGY: B Cells Spread and Gather.
M. M. Harnett (2006)
Science 312, 709-710
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882