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Erschienen in:
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2015 | Online First | Buchkapitel

Molecular Mechanisms of B Cell Antigen Gathering and Endocytosis

verfasst von : Robbert Hoogeboom, Pavel Tolar

Erschienen in: Current Topics in Microbiology and Immunology

Verlag: Springer International Publishing

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Abstract

Generation of high-affinity, protective antibodies requires B cell receptor (BCR) signaling, as well as antigen internalization and presentation to helper T cells. B cell antigen internalization is initiated by antigen capture, either from solution or from immune synapses formed on the surface of antigen-presenting cells, and proceeds via clathrin-dependent endocytosis and intracellular routing to late endosomes. Although the components of this pathway are still being discovered, it has become clear that antigen internalization is actively regulated by BCR signaling at multiple steps and, vice versa, that localization of the BCR along the endocytic pathway modulates signaling. Accordingly, defects in BCR internalization or trafficking contribute to enhanced B cell activation in models of autoimmune diseases and in B cell lymphomas. In this review, we discuss how BCR signaling complexes regulate each of the steps of this endocytic process and why defects along this pathway manifest as hyperactive B cell responses in vivo.
Literatur
Aluvihare VR, Khamlichi AA, Williams GT et al (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 16:3553–3562PubMedPubMedCentralCrossRef
Anitei M, Hoflack B (2012) Bridging membrane and cytoskeleton dynamics in the secretory and endocytic pathways. Nat Cell Biol 14:11–19CrossRef
Arana E, Vehlow A, Harwood NE et al (2008) Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation. Immunity 28:88–99PubMedCrossRef
Batista FD, Iber D, Neuberger MS (2001) B cells acquire antigen from target cells after synapse formation. Nature 411:489–494PubMedCrossRef
Becker-Herman S, Meyer-Bahlburg A, Schwartz MA et al (2011) WASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity. J Exp Med 208:2033–2042PubMedPubMedCentralCrossRef
Bonazzi M, Vasudevan L, Mallet A et al (2011) Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. J Cell Biol 195:525–536PubMedPubMedCentralCrossRef
Boulant S, Kural C, Zeeh J-C et al (2011) Actin dynamics counteract membrane tension during clathrin-mediated endocytosis. Nat Cell Biol 13:1124–1131PubMedPubMedCentralCrossRef
Burbage M, Keppler SJ, Gasparrini F et al (2014) Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity. J Exp Med 369:113
Busman-Sahay K, Drake L, Sitaram A et al (2013) Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs. PLoS ONE 8:e54938PubMedPubMedCentralCrossRef
Caballero A, Katkere B, Wen X-Y et al (2006) Functional and structural requirements for the internalization of distinct BCR-ligand complexes. Eur J Immunol 36:3131–3145PubMedCrossRef
Carrasco YR, Batista FD (2006a) B cell recognition of membrane-bound antigen: an exquisite way of sensing ligands. Curr Opin Immunol 18:286–291PubMedCrossRef
Carrasco YR, Batista FDA (2006b) B-cell activation by membrane-bound antigens is facilitated by the interaction of VLA-4 with VCAM-1. EMBO J 25:889–899PubMedPubMedCentralCrossRef
Carrasco YR, Batista FD (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 27:160–171PubMedCrossRef
Carrasco YR, Fleire SJ, Cameron T et al (2004) LFA-1/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation. Immunity 20:589–599PubMedCrossRef
Chatterjee P, Tiwari RK, Rath S et al (2012) Modulation of antigen presentation and B cell receptor signaling in B cells of beige mice. J Immunol 188:2695–2702PubMedCrossRef
Chaturvedi A, Dorward D, Pierce SK (2008) The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyper-responses to DNA-containing antigens. Immunity 28:799–809PubMedPubMedCentralCrossRef
Chaturvedi A, Martz R, Dorward D et al (2011) Endocytosed BCRs sequentially regulate MAPK and Akt signaling pathways from intracellular compartments. Nat Immunol 12:1119–1126PubMedPubMedCentralCrossRef
Cinamon G, Zachariah MA, Lam OM et al (2008) Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol 9:54–62PubMedCrossRef
Clark MR, Johnson SA, Cambier JC (1994) Analysis of Ig-α-tyrosine kinase interaction reveals two levels of binding specificity and tyrosine phosphorylated Ig-α stimulation of Fyn activity. EMBO J 13:1911–1919
Cyster JG (2010) B cell follicles and antigen encounters of the third kind. Nat Immunol 11:989PubMedCrossRef
Depoil D, Fleire S, Treanor BL et al (2008) CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand. Nat Immunol 9:63–72PubMedCrossRef
Dykstra ML, Longnecker R, Pierce SK (2001) Epstein-barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR. Immunity 14:57–67PubMedCrossRef
Ehrlich M, Boll W, Van Oijen A et al (2004) Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell 118:591–605PubMedCrossRef
Engqvist-Goldstein ÅEY, Kessels MM, Chopra VS et al (1999) An actin-binding protein of the Sla2/Huntingtin interacting protein 1 family is a novel component of clathrin-coated pits and vesicles. J Cell Biol 147:1503–1518PubMedPubMedCentralCrossRef
Ferguson AR, Youd ME, Corley RB (2004) Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells. Int Immunol 16:1411–1422PubMedCrossRef
Ferguson SM, Raimondi A, Paradise S et al (2009) Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev Cell 17:811–822PubMedPubMedCentralCrossRef
Fleire SJ, Goldman JP, Carrasco YR et al (2006) B cell ligand discrimination through a spreading and contraction response. Science 312:738–741PubMedCrossRef
Freeman SA, Lei V, Dang-Lawson M et al (2011) Cofilin-mediated F-actin severing is regulated by the rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation. J Immunol 187:5887–5900PubMedCrossRef
Gao J, Ma X, Gu W et al (2012) Novel functions of murine B1 cells: active phagocytic and microbicidal abilities. Eur J Immunol 42:982–992PubMedCrossRef
Gazumyan A, Reichlin A, Nussenzweig MC (2006) Ig β tyrosine residues contribute to the control of B cell receptor signaling by regulating receptor internalization. J Exp Med 203:1785–1794PubMedPubMedCentralCrossRef
Gonzalez SF, Lukacs-Kornek V, Kuligowski MP et al (2010) Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol 11:427–434PubMedPubMedCentralCrossRef
Granger E, McNee G, Allan V, Woodman P (2014) The role of the cytoskeleton and molecular motors in endosomal dynamics. Semin Cell Dev Biol 31:20–29PubMedPubMedCentralCrossRef
Haugh JM, Schooler K, Wells A et al (1999) Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-γ1 signaling pathway. J Biol Chem 274:8958–8965PubMedCrossRef
Heesters BA, Chatterjee P, Kim Y-A et al (2013) Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity 38:1164–1175PubMedPubMedCentralCrossRef
Itoh K, Shimono K, Lemmon V (2005) Dephosphorylation and internalization of cell adhesion molecule L1 induced by theta burst stimulation in rat hippocampus. Mol Cell Neurosci 29:245–249PubMedPubMedCentralCrossRef
Jackson LP, Kelly BT, McCoy AJ et al (2010) A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex. Cell 141:1220–1229PubMedPubMedCentralCrossRef
Jang C, Machtaler S, Matsuuchi L (2010) The role of Ig-α/β in B cell antigen receptor internalization. Immunol Lett 134:75–82PubMedCrossRef
Jean S, Cox S, Schmidt EJ et al (2012) Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling. Mol Biol Cell 23:2723–2740PubMedPubMedCentralCrossRef
Junt T, Moseman EA, Iannacone M et al (2007) Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450:110–114PubMedCrossRef
Katkere B, Rosa S, Drake JR (2012) The Syk-binding ubiquitin ligase c-Cbl mediates signaling-dependent B cell receptor ubiquitination and B cell receptor-mediated antigen processing and presentation. J Biol Chem 287:16636–16644PubMedPubMedCentralCrossRef
Kitaura Y, Jang IK, Wang Y et al (2007) Control of the B cell-intrinsic tolerance programs by ubiquitin ligases Cbl and Cbl-b. Immunity 26:567–578PubMedPubMedCentralCrossRef
Li J, Barreda DR, Zhang Y-A et al (2006) B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities. Nat Immunol 7:1116–1124PubMedCrossRef
Lin KBL, Freeman SA, Zabetian S et al (2008) The rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands. Immunity 28:75–87PubMedCrossRef
Liu AP, Aguet F, Danuser G, Schmid SL (2010) Local clustering of transferrin receptors promotes clathrin-coated pit initiation. J Cell Biol 191:1381–1393PubMedPubMedCentralCrossRef
Ma H, Yankee TM, Hu J et al (2001) Visualization of Syk-antigen receptor interactions using green fluorescent protein: differential roles for Syk and Lyn in the regulation of receptor capping and internalization. J Immunol 166:1507–1516PubMedCrossRef
Malhotra S, Kovats S, Zhang W, Coggeshall KM (2009) Vav and Rac activation in B cell antigen receptor endocytosis involves Vav recruitment to the adapter protein LAB. J Biol Chem 284:36202–36212PubMedPubMedCentralCrossRef
Martin F, Oliver AM, Kearney JF (2001) Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14:617–629PubMedCrossRef
Matsumoto M, Oyamada K, Takahashi H et al (2009) Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways. Proteomics 9:3549–3563PubMedCrossRef
McLeod SJ, Ingham RJ, Bos JL et al (1998) Activation of the Rap1 GTPase by the B cell antigen receptor. J Biol Chem 273:29218–29223PubMedCrossRef
Miaczynska M, Christoforidis S, Giner A et al (2004) APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell 116:445–456PubMedCrossRef
Minden MD-V, Übelhart R, Schneider D et al (2013) Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature 489:309–312CrossRef
Monks C, Freiberg B, Kupfer H et al (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395:82–86PubMedCrossRef
Ngo VN, Young RM, Schmitz R et al (2012) Oncogenically active MYD88 mutations in human lymphoma. Nature 469:115–119
Niiro H, Allam A, Stoddart A et al (2004) The B lymphocyte adaptor molecule of 32 kilodaltons (Bam32) regulates B cell antigen receptor internalization. J Immunol 173:5601–5609PubMedCrossRef
Onabajo OO, Seeley MK, Kale A et al (2008) Actin-binding protein 1 regulates B cell receptor-mediated antigen processing and presentation in response to B cell receptor activation. J Immunol 180:6685–6695PubMedCrossRef
O’Neill S, Veselits M, Zhang M et al (2009) Endocytic sequestration of the B cell antigen receptor and toll-like receptor 9 in anergic cells. PNAS 106:6262–6267PubMedPubMedCentralCrossRef
O’Neill SK, Getahun A, Gauld SB et al (2011) Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy. Immunity 35:746–756PubMedPubMedCentralCrossRef
Pape KA, Catron DM, Itano AA, Jenkins MK (2007) The humoral immune response is initiated in lymph nodes by B cells that acquire soluble antigen directly in the follicles. Immunity 26:491–502PubMedCrossRef
Parameswaran N, Enyindah-Asonye G, Bagheri N et al (2013) Spatial coupling of JNK activation to the B cell antigen receptor by tyrosine-phosphorylated ezrin. J Immunol 190:2017–2026PubMedCrossRef
Phan TG, Grigorova I, Okada T, Cyster JG (2007) Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells. Nat Immunol 8:992–1000PubMedCrossRef
Pore D, Pore D, Parameswaran N et al (2013) Ezrin tunes the magnitude of humoral immunity. J Immunol 191:4048–4058PubMedCrossRef
Posor Y, Eichhorn-Gruenig M, Puchkov D et al (2013) Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499:233–237PubMedCrossRef
Puga I, Cols M, Barra CM et al (2012) B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol 13:170–180CrossRef
Qi H, Egen JG, Huang AYC, Germain RN (2006) Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 312:1672–1676PubMedCrossRef
Randall KL, Lambe T, Johnson A et al (2009) Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production. Nat Immunol 10:1283–1291PubMedPubMedCentralCrossRef
Roozendaal R, Mempel TR, Pitcher LA et al (2009) Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30:264–276PubMedPubMedCentralCrossRef
Saez de Guinoa J, Barrio L, Carrasco YR (2013) Vinculin arrests motile B cells by stabilizing integrin clustering at the immune synapse. J Immunol 191:2742–2751PubMedCrossRef
Sáez de Guinoa J, Barrio L, Mellado M, Carrasco YR (2011) CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics. Blood 118:1560–1569PubMedCrossRef
Satpathy S, Wagner SA, Beli P, et al (2015) Systems-wide analysis of the BCR signaling complexes and the downstream phosphorylation and ubiquitylation. Mol Syst Biol 11:810
Schnyder T, Castello A, Feest C et al (2011) B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3to recruit dynein to the signaling microcluster. Immunity 34:905–918PubMedCrossRef
Schwickert TA, Victora GD, Fooksman DR et al (2011) A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center. J Exp Med 208:1243–1252PubMedPubMedCentralCrossRef
Seeley-Fallen MK, Liu LJ, Shapiro MR et al (2014) Actin-binding protein 1 links B-cell antigen receptors to negative signaling pathways. PNAS 111:9881–9886PubMedPubMedCentralCrossRef
Sharma S, Orlowski G, Song W (2009) Btk regulates B cell receptor-mediated antigen processing and presentation by controlling actin cytoskeleton dynamics in B cells. J Immunol 182:329–339PubMedCrossRef
Shih T-AY, Meffre E, Roederer M, Nussenzweig MC (2002) Role of BCR affinity in T cell dependent antibody responses in vivo. Nat Immunol 3:570–575PubMedCrossRef
Shin H-W, Hayashi M, Christoforidis S et al (2005) An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J Cell Biol 170:607–618PubMedPubMedCentralCrossRef
Sohn HW, Gu H, Pierce SK (2003) Cbl-b negatively regulates B cell antigen receptor signaling in mature B cells through ubiquitination of the tyrosine kinase Syk. J Exp Med 197:1511–1524PubMedPubMedCentralCrossRef
Song W, Liu C, Seeley-Fallen MK et al (2013) Actin-mediated feedback loops in B-cell receptor signaling. Immunol Rev 256:177–189PubMedCrossRef
Souwer Y, Griekspoor A, Jorritsma T et al (2009) B cell receptor-mediated internalization of salmonella: a novel pathway for autonomous B cell activation and antibody production. J Immunol 182:7473–7481PubMedCrossRef
Stoddart A, Dykstra ML, Brown BK et al (2002) Lipid rafts unite signaling cascades with clathrin to regulate BCR internalization. Immunity 17:451–462PubMedCrossRef
Stoddart A, Jackson AP, Brodsky F (2005) Plasticity of B cell receptor internalization upon conditional depletion of clathrin. Mol Biol Cell 16:2339–2348PubMedPubMedCentralCrossRef
Suzuki K, Grigorova I, Phan TG et al (2009) Visualizing B cell capture of cognate antigen from follicular dendritic cells. J Exp Med 206:1485–1493PubMedPubMedCentralCrossRef
Tanno H, Yamaguchi T, Goto E et al (2012) The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane. Mol Biol Cell 23:1343–1353PubMedPubMedCentralCrossRef
Tolar P, Spillane KM (2014) Force generation in B-cell synapses: mechanisms coupling B-cell receptor binding to antigen internalization and affinity discrimination. Adv Immunol 123:69–100
Tolar P, Hanna J, Krueger PD, Pierce SK (2009) The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens. Immunity 30:44–55PubMedPubMedCentralCrossRef
Treanor B, Depoil D, Bruckbauer A, Batista FD (2011) Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity. J Exp Med 208:1055–1068PubMedPubMedCentralCrossRef
Veselits M, Tanaka A, Lipkowitz S et al (2014) Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to toll-like receptor 9 activation in late endosomes. PLoS ONE 9:e89792PubMedPubMedCentralCrossRef
Victora GD, Schwickert TA, Fooksman DR et al (2010) Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143:592–605PubMedPubMedCentralCrossRef
Weber M, Treanor B, Depoil D et al (2008) Phospholipase C-γ2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen. J Exp Med 205:853–868PubMedPubMedCentralCrossRef
Yuseff M-I, Reversat A, Lankar D et al (2011) Polarized secretion of lysosomes at the B cell synapse couples antigen extraction to processing and presentation. Immunity 35:361–374PubMedCrossRef
Zhang M, Veselits M, O’Neill S et al (2007) Ubiquitinylation of Igβ dictates the endocytic fate of the B cell antigen receptor. J Immunol 179:4435–4443PubMedCrossRef
Zoncu R, Perera RM, Balkin DM et al (2009) A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes. Cell 136:1110–1121PubMedPubMedCentralCrossRef
Metadaten
Titel
Molecular Mechanisms of B Cell Antigen Gathering and Endocytosis
verfasst von
Robbert Hoogeboom
Pavel Tolar
Copyright-Jahr
2015
Verlag
Springer International Publishing
DOI
https://doi.org/10.1007/82_2015_476