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Visualizing the Molecular and Cellular Events Underlying the Initiation of B-Cell Activation

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 334))

Abstract

The appropriate activation of B cells is critical for the development of effective immune responses. B cell activation is initiated following the engagement of the B cell receptor (BCR) with specific antigen. The spatiotemporal characterization of the ensuing molecular and cellular events has been the subject of recent high-resolution imaging investigations. In this review we highlight information gathered thus far concerning the initial processes underlying the activation of B cells. First, we consider studies that have offered new insights into the early molecular events that occur within the B cell prior to formation of the immunological synapse. As such, BCR-microclusters formed on engagement with antigen have been identified as the sites of active signaling and assembly of “microsignalosomes.” Furthermore, signaling through these “microsignalosomes” is propagated and enhanced through B cell spreading in response to membrane-antigen in a CD19-dependent manner. Finally, we discuss a number of multiphoton microscopy studies that have enabled dynamic characterization of the initial encounters between B cells and antigen in vivo. These investigations visualize the presentation of larger antigens to B cells via cell-mediated strategies, involving macrophages in the subcapsular sinus and dendritic cells in the paracortex.

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References

  • Ahearn J, Fischer M, Croix D, Goerg S, Ma M, Xia J, Zhou X, Howard R, Rothstein T, Carroll M (1996) Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B-cell response to T-dependent antigen. Immunity 4:251–262

    Article  PubMed  CAS  Google Scholar 

  • Allen C, Okada T, Tang H, Cyster J (2007) Imaging of germinal center selection events during affinity maturation. Science 315:528–531

    Article  PubMed  CAS  Google Scholar 

  • Aluvihare VR, Khamlichi AA, Williams GT, Adorini L, Neuberger MS (1997) Acceleration of intracellular targeting of antigen by the B-cell antigen receptor: importance depends on the nature of the antigen-antibody interaction. EMBO J 16:3553–3562

    Article  PubMed  CAS  Google Scholar 

  • Amigorena S, Drake JR, Webster P, Mellman I (1994) Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes. Nature 369:113–120

    Article  PubMed  CAS  Google Scholar 

  • Arana E, Vehlow A, Harwood N, Vigorito E, Henderson R, Turner M, Tybulewicz V, Batista F (2008) Activation of the small GTPase Rac2 via the B-cell receptor regulates B-cell adhesion and immunological synpase formation. Immunity 28:88–99

    Article  PubMed  CAS  Google Scholar 

  • Bajénoff M, Germain R (2007) Seeing is believing: a focus on the contribution of microscopic imaging to our understanding of immune system function. Eur J Immunol 37(Suppl 1):S18–S33

    Article  PubMed  CAS  Google Scholar 

  • Bajénoff M, Egen J, Koo L, Laugier J, Brau F, Glaichenhaus N, Germain R (2006) Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001

    Article  PubMed  CAS  Google Scholar 

  • Batista F, Neuberger M (2000) B-cells extract and present immobilized antigen: implications for affinity discrimination. EMBO J 19:513–20

    Article  PubMed  CAS  Google Scholar 

  • Batista F, Iber D, Neuberger M (2001) B-cells acquire antigen from targeT-cells after synapse formation. Nature 411:489–494

    Article  PubMed  CAS  Google Scholar 

  • Batista FD, Arana E, Barral P, Carrasco YR, Depoil D, Eckl-Dorna J, Fleire S, Howe K, Vehlow A, Weber M, Treanor B (2007). The role of intergrins and coreceptors in refining thresholds for B-cell responses. Immunol Rev 218:197–213

    Article  PubMed  CAS  Google Scholar 

  • Bousso P, Robey E (2003) Dynamics of CD8+ T-cell priming by dendritic cells in intact lymph nodes. Nat Immunol 4:579–585

    Article  PubMed  CAS  Google Scholar 

  • Brink R, Phan TG, Paus D, Chan TD (2008) Visualizing the effects of antigen affinity on T-dependent B-cell differentiation. Immunol Cell Biol 86:31–39

    Article  PubMed  CAS  Google Scholar 

  • Brown J, De Jesus D, Holborow E, Harris G (1970) Lymphocyte-mediated transport of aggregated human gamma-globulin into germinal center areas of normal mouse spleen. Nature 228:367–369

    Article  PubMed  CAS  Google Scholar 

  • Bunnell S, Kapoor V, Trible R, Zhang W, Samelson L (2001) Dynamic actin polymerization drives T-cell receptor-induced spreading: a role for the signal transduction adaptor LAT. Immunity 14:315–329

    Article  PubMed  CAS  Google Scholar 

  • Bunnell S, Hong D, Kardon J, Yamazaki T, McGlade C, Barr V, Samelson L (2002) T-cell receptor ligation induces the formation of dynamically regulated signaling assemblies. J Cell Biol 158:1263–1275

    Article  PubMed  CAS  Google Scholar 

  • Bunnell S, Singer A, Hong D, Jacque B, Jordan M, Seminario M, Barr V, Koretzky G, Samelson L (2006) Persistence of cooperatively stabilized signaling clusters drives T-cell activation. Mol Cell Biol 26:7155–7166

    Article  PubMed  CAS  Google Scholar 

  • Cahalan M, Parker I (2008) Choreography of Cell Motility and Interaction Dynamics Imaged by Two-Photon Microscopy in Lymphoid Organs. Annu Rev Immunol 26:585–626

    Article  PubMed  CAS  Google Scholar 

  • Campi G, Varma R, Dustin M (2005) Actin and agonist MHC-peptide complex-dependent T-cell receptor microclusters as scaffolds for signaling. J Exp Med 202:1031–1036

    Article  PubMed  CAS  Google Scholar 

  • Carrasco YR, Batista FD (2006a) B-cell recognition of membrane-bound antigen: an exquisite way of sensing ligands. Curr Opin Immunol 18:286–291

    Article  CAS  Google Scholar 

  • Carrasco YR, Batista FD (2006b) B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1. EMBO J 25:889–899

    Article  CAS  Google Scholar 

  • Carrasco Y, Batista F (2007) B-cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 27:160–171

    Article  PubMed  CAS  Google Scholar 

  • Carrasco Y, Fleire S, Cameron T, Dustin M, Batista F (2004) LFA-1/ICAM-1 interaction lowers the threshold of B-cell activation by facilitating B-cell adhesion and synapse formation. Immunity 20:589–599

    Article  PubMed  CAS  Google Scholar 

  • Carroll M (1998) The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 16:545–568

    Article  PubMed  CAS  Google Scholar 

  • Catron D, Itano A, Pape K, Mueller D, Jenkins M (2004) Visualizing the first 50 hr of the primary immune response to a soluble antigen. Immunity 21:341–347

    Article  PubMed  CAS  Google Scholar 

  • Cemerski S, Das J, Giurisato E, Markiewicz MA, Allen PM, Chakraborty AK, Shaw AS (2008) The balance between T-cell receptor signaling and degradation at the center of the immunological synapse is determined by antigen quality. Immunity 29:414–422

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Frank A, Adams J, Steinman R (1978) Distribution of horseradish peroxidase (HRP)-anti-HRP immune complexes in mouse spleen with special reference to follicular dendritic cells. J Cell Biol 79:184–199

    Article  PubMed  CAS  Google Scholar 

  • Choudhuri K, Wiseman D, Brown M, Gould K, van der Merwe P (2005) T-cell receptor triggering is critically dependent on the dimensions of its peptide-MHC ligand. Nature 436:578–582

    Article  PubMed  CAS  Google Scholar 

  • Cinamon G, Zachariah M, Lam O, Foss F, Cyster J (2007) Follicular shuttling of marginal zone B-cells facilitates antigen transport. Nat Immunol 9:54–62

    Article  PubMed  CAS  Google Scholar 

  • Clark S (1962) The reticulum of lymph nodes in mice studied with the electron microscope. Am J Anat 110:217–257

    Article  PubMed  Google Scholar 

  • Colino J, Shen Y, Snapper C (2002) Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms. J Exp Med 195:1–13

    Article  PubMed  CAS  Google Scholar 

  • Cyster J, Ansel K, Reif K, Ekland E, Hyman P, Tang H, Luther S, Ngo V (2000) Follicular stromal cells and lymphocyte homing to follicles. Immunol Rev 176:181–193

    Article  PubMed  CAS  Google Scholar 

  • Dal Porto J, Gauld S, Merrell K, Mills D, Pugh-Bernard A, Cambier J (2004) B-cell antigen receptor signaling 101. Mol Immunol 41:599–613

    Article  PubMed  CAS  Google Scholar 

  • Davis S, van der Merwe P (1996) The structure and ligand interactions of CD2: implications for T-cell function. Immunol Today 17:177–187

    Article  PubMed  CAS  Google Scholar 

  • Davis S, van der Merwe P (2006) The kinetic-segregation model: TCR triggering and beyond. Nat Immunol 7:803–809

    Article  PubMed  CAS  Google Scholar 

  • Davis D, Chiu I, Fassett M, Cohen G, Mandelboim O, Strominger J (1999) The human natural killer cell immune synapse. Proc Natl Acad Sci USA 96:15062–15067

    Article  PubMed  CAS  Google Scholar 

  • DeFranco A (1997) The complexity of signaling pathways activated by the BCR. Curr Opin Immunol 9:296–308

    Article  PubMed  CAS  Google Scholar 

  • Delamarre L, Pack M, Chang H, Mellman I, Trombetta E (2005) Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 307:1630–1634

    Article  PubMed  CAS  Google Scholar 

  • Depoil D, Fleire S, Treanor BL, Weber M, Harwood NE, Marchbank KL, Tybulewicz VL, Batista FD (2008) CD19 is essential for B-cell activation by promoting B-cell receptor-antigen microcluster formation in response to membrane-bound ligand. Nat Immunol 9:63–72

    Article  PubMed  CAS  Google Scholar 

  • Dudziak D, Kamphorst A, Heidkamp G, Buchholz V, Trumpfheller C, Yamazaki S, Cheong C, Liu K, Lee H, Park C, Steinman R, Nussenzweig M (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315:107–111

    Article  PubMed  CAS  Google Scholar 

  • Engel P, Zhou L, Ord D, Sato S, Koller B, Tedder T (1995) Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3:39–50

    Article  PubMed  CAS  Google Scholar 

  • Farr A, Cho Y, De Bruyn P (1980) The structure of the sinus wall of the lymph node relative to its endocytic properties and transmural cell passage. Am J Anat 157:265–284

    Article  PubMed  CAS  Google Scholar 

  • Fearon D, Carroll M (2000) Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu Rev Immunol 18:393–422

    Article  PubMed  CAS  Google Scholar 

  • Fearon D, Carter R (1995) The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu Rev Immunol 13:127–149

    Article  PubMed  CAS  Google Scholar 

  • Fleire S, Goldman J, Carrasco Y, Weber M, Bray D, Batista F (2006) B-cell ligand discrimination through a spreading and contraction response. Science 312:738–741

    Article  PubMed  CAS  Google Scholar 

  • Fossum S (1980) The architecture of rat lymph nodes. IV. Distribution of ferritin and colloidal carbon in the draining lymph nodes after foot-pad injection. Scand J Immunol 12:433–441

    Article  PubMed  CAS  Google Scholar 

  • Fu C, Turck C, Kurosaki T, Chan A (1998) BLNK: a central linker protein in B-cell activation. Immunity 9:93–103

    Article  PubMed  CAS  Google Scholar 

  • Fujimoto M, Bradney A, Poe J, Steeber D, Tedder T (1999) Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop. Immunity 11:191–200

    Article  PubMed  CAS  Google Scholar 

  • Garside P, Ingulli E, Merica R, Johnson J, Noelle R, Jenkins M (1998) Visualization of specific B and T lymphocyte interactions in the lymph node. Science 281:96–99

    Article  PubMed  CAS  Google Scholar 

  • Germain R, Miller M, Dustin M, Nussenzweig M (2006) Dynamic imaging of the immune system: progress, pitfalls and promise. Nat Rev Immunol 6:497–507

    Article  PubMed  CAS  Google Scholar 

  • Goitsuka R, Fujimura Y, Mamada H, Umeda A, Morimura T, Uetsuka K, Doi K, Tsuji S, Kitamura D (1998) BASH, a novel signaling molecule preferentially expressed in B-cells of the bursa of Fabricius. J Immunol 161:5804–5808

    PubMed  CAS  Google Scholar 

  • Goodnow CC (1992) Transgenic mice and analysis of B-cell tolerance. Annu Rev Immunol 10:489–518

    Article  PubMed  CAS  Google Scholar 

  • Goodnow C, Crosbie J, Adelstein S, Lavoie T, Smith-Gill S, Brink R, Pritchard-Briscoe H, Wotherspoon J, Loblay R, Raphael K (1988) Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334:676–682

    Article  PubMed  CAS  Google Scholar 

  • Grakoui A, Bromley S, Sumen C, Davis M, Shaw A, Allen P, Dustin M (1999) The immunological synapse: a molecular machine controlling T-cell activation. Science 285:221–227

    Article  PubMed  CAS  Google Scholar 

  • Gray D, Kumararatne D, Lortan J, Khan M, MacLennan I (1984) Relation of intra-splenic migration of marginal zone B-cells to antigen localization on follicular dendritic cells. Immunology 52:659–669

    PubMed  CAS  Google Scholar 

  • Gretz J, Anderson A, Shaw S (1997) Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol Rev 156:11–24

    Article  PubMed  CAS  Google Scholar 

  • Gretz J, Norbury C, Anderson A, Proudfoot A, Shaw S (2000) Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J Exp Med 192:1425–1440

    Article  PubMed  CAS  Google Scholar 

  • Harwood NE, Batista FD (2008) New insights into the early molecular events underlying B-cell activation. Immunity 28:609–619

    Article  PubMed  CAS  Google Scholar 

  • Hauser A, Junt T, Mempel T, Sneddon M, Kleinstein S, Henrickson S, von Andrian U, Shlomchik M, Haberman A (2007) Definition of germinal-center B-cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity 26:655–667

    Article  PubMed  CAS  Google Scholar 

  • Hjelm F, Karlsson M, Heyman B (2008) A novel B-cell-mediated transport of IgE-immune complexes to the follicle of the spleen. J Immunol 180:6604–6610

    PubMed  CAS  Google Scholar 

  • Irvine DJ, Purbhoo MA, Krogsgaard M, Davis MM (2002). Driect observation of ligand recognition by T cells. Nature 419:845–849

    Article  PubMed  CAS  Google Scholar 

  • Itano A, McSorley S, Reinhardt R, Ehst B, Ingulli E, Rudensky A, Jenkins M (2003) Distinct dendritic cell populations sequentially present antigen to CD4 T-cells and stimulate different aspects of cell-mediated immunity. Immunity 19:47–57

    Article  PubMed  CAS  Google Scholar 

  • Junt T, Moseman E, Iannacone M, Massberg S, Lang P, Boes M, Fink K, Henrickson S, Shayakhmetov D, Di Paolo N, van Rooijen N, Mempel T, Whelan S, von Andrian U (2007) Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B-cells. Nature 450:110–114

    Article  PubMed  CAS  Google Scholar 

  • Klaus G, Humphrey J (1977) The generation of memory cells. I. The role of C3 in the generation of B memory cells. Immunology 33:31–40

    PubMed  CAS  Google Scholar 

  • Klaus G, Humphrey J, Kunkl A, Dongworth D (1980) The follicular dendritic cell: its role in antigen presentation in the generation of immunological memory. Immunol Rev 53:3–28

    Article  PubMed  CAS  Google Scholar 

  • Kurosaki T (1999) Genetic analysis of B-cell antigen receptor signaling. Annu Rev Immunol 17:555–592

    Article  PubMed  CAS  Google Scholar 

  • Kurosaki T, Kurosaki M (1997) Transphosphorylation of Bruton’s tyrosine kinase on tyrosine 551 is critical for B-cell antigen receptor function. J Biol Chem 272:15595–15598

    Article  PubMed  CAS  Google Scholar 

  • Lanzavecchia A (1985) Antigen-specific interaction between T and B-cells. Nature 314:537–539

    Article  PubMed  CAS  Google Scholar 

  • Lee K, Holdorf A, Dustin M, Chan A, Allen P, Shaw A (2002) T-cell receptor signaling precedes immunological synapse formation. Science 295:1539–1542

    Article  PubMed  CAS  Google Scholar 

  • Li X, Sandoval D, Freeberg L, Carter R (1997) Role of CD19 tyrosine 391 in synergistic activation of B lymphocytes by coligation of CD19 and membrane Ig. J Immunol 158:5649–5657

    PubMed  CAS  Google Scholar 

  • Lichtman J, Conchello J (2005) Fluorescence microscopy. Nat Methods 2:910–919

    Article  PubMed  CAS  Google Scholar 

  • Lillemeier BF, Pfeiffer JR, Surviladze Z, Wilson BS, Davis MM (2006) Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Proc Natl Acad Sci U S A 103:18992–18997

    Article  PubMed  CAS  Google Scholar 

  • Lin K, Freeman S, Zabetian S, Brugger H, Weber M, Lei V, Dang-Lawson M, Tse K, Santamaria R, Batista F, Gold M (2008) The Rap GTPases regulate B-cell morphology, immune synpase formation and signaling by particulate B-cell receptor ligands. Immunity 28:75–87

    Article  PubMed  CAS  Google Scholar 

  • Lindquist R, Shakhar G, Dudziak D, Wardemann H, Eisenreich T, Dustin M, Nussenzweig M (2004) Visualizing dendritic cell networks in vivo. Nat Immunol 5:1243–1250

    Article  PubMed  CAS  Google Scholar 

  • MacLennan I (1994) Germinal centers. Annu Rev Immunol 12:117–139

    Article  PubMed  CAS  Google Scholar 

  • MacLennan I, Toellner K, Cunningham A, Serre K, Sze D, Zuniga E, Cook M, Vinuesa C (2003) Extrafollicular antibody responses. Immunol Rev 194:8–18

    Article  PubMed  CAS  Google Scholar 

  • Mandel T, Phipps R, Abbot A, Tew J (1980) The follicular dendritic cell: long term antigen retention during immunity. Immunol Rev 53:29–59

    Article  PubMed  CAS  Google Scholar 

  • Miller M, Wei S, Parker I, Cahalan M (2002) Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296:1869–1873

    Article  PubMed  CAS  Google Scholar 

  • Moller G (1987) Role of somatic mutation in the generation of lymphocyte diversity. Immunol Rev 96:1–162

    Google Scholar 

  • Monks C, Freiberg B, Kupfer H, Sciaky N, Kupfer A (1998) Three-dimensional segregation of supramolecular activation clusters in T-cells. Nature 395:82–86

    Article  PubMed  CAS  Google Scholar 

  • Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD (1996) Polarity of T-cell shape, motility, and sensitivity to antigen. Immunity 4:421–430

    Article  PubMed  CAS  Google Scholar 

  • Nossal G, Abbot A, Mitchell J, Lummus Z (1968) Antigens in immunity. XV. Ultrastructural features of antigen capture in primary and secondary lymphoid follicles. J Exp Med 127:277–290

    Article  PubMed  CAS  Google Scholar 

  • Okada T, Miller M, Parker I, Krummel M, Neighbors M, Hartley S, O’Garra A, Cahalan M, Cyster J (2005) Antigen-engaged B-cells undergo chemotaxis toward the T zone and form motile conjugates with helper T-cells. PLoS Biol 3:e150

    Article  PubMed  CAS  Google Scholar 

  • Pape K, Catron D, Itano A, Jenkins M (2007) The humoral immune response is initiated in lymph nodes by B-cells that acquire soluble antigen directly in the follicles. Immunity 26:491–502

    Article  PubMed  CAS  Google Scholar 

  • Parsey M, Lewis G (1993) Actin polymerization and pseudopod reorganization accompany anti-CD3-induced growth arrest in Jurkat T-cells. J Immunol 151:1881–1893

    PubMed  CAS  Google Scholar 

  • Pelanda R, Schwers S, Sonoda E, Torres RM, Nemazee D, Rajewsky K (1997) Receptor editing in a transgenic mouse model: site, efficiency, and role in B-cell tolerance and antibody diversification. Immunity 7:765–775

    Article  PubMed  CAS  Google Scholar 

  • Pesando JM, Bouchard LS, McMaster BE (1989) CD19 is functionally and physically associated with surface immunoglobulin. J Exp Med 170:2159–2164

    Article  PubMed  CAS  Google Scholar 

  • Phan TG, Amesbury M, Gardam S, Crosbie J, Hasbold J, Hodgkin PD, Basten A, Brink R (2003) B-cell receptor-independent stimuli trigger immunoglobulin (Ig) class switch recombination and production of IgG autoantibodies by anergic self-reactive B-cells. J Exp Med 197:845–860

    Article  PubMed  CAS  Google Scholar 

  • Phan T, Grigorova I, Okada T, Cyster J (2007) Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B-cells. Nat Immunol 8:992–1000

    Article  PubMed  CAS  Google Scholar 

  • Phee H, Rodgers W, Coggeshall KM (2001) Visualization of negative signaling in B-cells by quantitative confocal microscopy. Mol Cell Biol 21:8615–8625

    Article  PubMed  CAS  Google Scholar 

  • Qi H, Egen JG, Huang AY, Germain RN (2006) Extrafollicular activation of lymph node B-cells by antigen-bearing dendritic cells. Science 312:1672–1676

    Article  PubMed  CAS  Google Scholar 

  • Qin D, Wu J, Vora K, Ravetch J, Szakal A, Manser T, Tew J (2000) Fc gamma receptor IIB on follicular dendritic cells regulates the B-cell recall response. J Immunol 164:6268–6275

    PubMed  CAS  Google Scholar 

  • Reth M (1989) Antigen receptor tail clue. Nature 338:383–384

    Article  PubMed  CAS  Google Scholar 

  • Reth M, Wienands J (1997) Initiation and processing of signals from the B-cell antigen receptor. Annu Rev Immunol 15:453–479

    Article  PubMed  CAS  Google Scholar 

  • Rickert R, Rajewsky K, Roes J (1995) Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature 376:352–355

    Article  PubMed  CAS  Google Scholar 

  • Rock K, Benacerraf B, Abbas A (1984) Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J Exp Med 160:1102–1113

    Article  PubMed  CAS  Google Scholar 

  • Russell DM, DembiZ, Morahan G, Miller JF, Bürki K, Nemazee D (1991) Peripheral deletion of self-reactive B-cells. Nature 354:308–311

    Article  PubMed  CAS  Google Scholar 

  • Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179:1109–1118

    Article  PubMed  CAS  Google Scholar 

  • Sato S, Miller A, Howard M, Tedder T (1997) Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19. J Immunol 159:3278–3287

    PubMed  CAS  Google Scholar 

  • Schamel W, Reth M (2000) Monomeric and oligomeric complexes of the B-cell antigen receptor. Immunity 13:5–14

    Article  PubMed  CAS  Google Scholar 

  • Scharenberg A, Humphries L, Rawlings D (2007) Calcium signalling and cell-fate choice in B-cells. Nat Rev Immunol 7:778–789

    Article  PubMed  CAS  Google Scholar 

  • Schneckenburger H (2005) Total internal reflection fluorescence microscopy: technical innovations and novel applications. Curr Opin Biotechnol 16:13–18

    Article  PubMed  CAS  Google Scholar 

  • Schreiner GF, Braun J, Unanue ER (1976) Spontaneous redistribution of surface immunoglobulin in the motile B lymphocyte. J Exp Med 144:1683–1688

    Article  PubMed  CAS  Google Scholar 

  • Schwickert T, Lindquist R, Shakhar G, Livshits G, Skokos D, Kosco-Vilbois M, Dustin M, Nussenzweig M (2007) In vivo imaging of germinal centers reveals a dynamic open structure. Nature 446:83–87

    Article  PubMed  CAS  Google Scholar 

  • Shinohara H, Kurosaki T (2006) Genetic analysis of B-cell signaling. Subcell Biochem 40:145–187

    PubMed  Google Scholar 

  • Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt D, Pabst R, Lutz M, Sorokin L (2005) The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T-cell area of the lymph node. Immunity 22:19–29

    Article  PubMed  CAS  Google Scholar 

  • Stackpole CW, Jacobson JB, Lardis MP (1974) Two distinct types of capping of surface receptors on mouse lymphoid cells. Nature 248:232–234

    Article  PubMed  CAS  Google Scholar 

  • Stinchcombe J, Bossi G, Booth S, Griffiths G (2001) The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15:751–761

    Article  PubMed  CAS  Google Scholar 

  • Stoll S, Delon J, Brotz T, Germain R (2002) Dynamic imaging of T-cell-dendritic cell interactions in lymph nodes. Science 296:1873–1876

    Article  PubMed  Google Scholar 

  • Szakal A, Holmes K, Tew J (1983) Transport of immune complexes from the subcapsular sinus to lymph node follicles on the surface of nonphagocytic cells, including cells with dendritic morphology. J Immunol 131:1714–1727

    PubMed  CAS  Google Scholar 

  • Szakal A, Kosco M, Tew J (1989) Microanatomy of lymphoid tissue during humoral immune responses: structure function relationships. Annu Rev Immunol 7:91–109

    Article  PubMed  CAS  Google Scholar 

  • Tew J, Mandel T, Burgess A, Hicks J (1979) The antigen binding dendritic cell of the lymphoid follicles: evidence indicating its role in the maintenance and regulation of serum antibody levels. Adv Exp Med Biol 114:407–410

    PubMed  CAS  Google Scholar 

  • Tew J, Phipps R, Mandel T (1980) The maintenance and regulation of the humoral immune response: persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells. Immunol Rev 53:175–201

    Article  PubMed  CAS  Google Scholar 

  • Tolar P, Sohn H, Pierce S (2005) The initiation of antigen-induced B-cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer. Nat Immunol 6:1168–1176

    Article  PubMed  CAS  Google Scholar 

  • Treanor B, Batista F (2007) Mechanistic insight into lymphocyte activation through quantitative imaging and theoretical modelling. Curr Opin Immunol 19:476–483

    Article  PubMed  CAS  Google Scholar 

  • Tuveson D, Carter R, Soltoff S, Fearon D (1993) CD19 of B-cells as a surrogate kinase insert region to bind phosphatidylinositol 3-kinase. Science 260:986–989

    Article  PubMed  CAS  Google Scholar 

  • Unanue ER, Perkins WD, Karnovsky MJ (1972) Ligand-induced movement of lymphocyte membrane macromolecules. I. Analysis by immunofluorescence and ultrastructural radioautography. J Exp Med 136:885–906

    Article  PubMed  CAS  Google Scholar 

  • van Ewijk W, Brekelmans P, Jacobs R, Wisse E (1988) Lymphoid microenvironments in the thymus and lymph node. Scann Microsc 2:2129–2140

    CAS  Google Scholar 

  • Weber M, Treanor B, Depoil D, Shinohara H, Harwood NE, Hikida M, Kurosaki T, Batista FD (2008) Phospholipase C-gamma2 and Vav cooperate within signaling microclusters to propagate B-cell spreading in response to membrane-bound antigen. J Exp Med 205:853–868

    Article  PubMed  CAS  Google Scholar 

  • Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen P, Reth M (1998) SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J Exp Med 188:791–795

    Article  PubMed  CAS  Google Scholar 

  • Winding P, Berchtold MW (2001) The chicken B-cell line DT40: a novel tool for gene disruption experiments. J Immunol Methods 249:1–16

    Article  PubMed  CAS  Google Scholar 

  • Wykes M, Pombo A, Jenkins C, MacPherson G (1998) Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response. J Immunol 161:1313–1319

    PubMed  CAS  Google Scholar 

  • Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, Dustin M, Saito T (2005) Newly generated T-cell receptor microclusters initiate and sustain T-cell activation by recruitment of Zap70 and SLP-76. Nat Immunol 6:1253–1262

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank members of the Lymphocyte Interaction Laboratory for helpful discussions and critical reading of the manuscript.

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Correspondence to Facundo D. Batista .

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© 2009 Springer-Verlag Berlin Heidelberg

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Harwood, N.E., Batista, F.D. (2009). Visualizing the Molecular and Cellular Events Underlying the Initiation of B-Cell Activation. In: Dustin, M., McGavern, D. (eds) Visualizing Immunity. Current Topics in Microbiology and Immunology, vol 334. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-93864-4_7

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