1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 37, 2019
  5. Article

Annual Review of Immunology

Volume 37, 2019

Antigen Receptor Function in the Context of the Nanoscale Organization of the B Cell Membrane

Abstract

The B cell antigen receptor (BCR) plays a central role in the self/nonself selection of B lymphocytes and in their activation by cognate antigen during the clonal selection process. It was long thought that most cell surface receptors, including the BCR, were freely diffusing and randomly distributed. Since the advent of superresolution techniques, it has become clear that the plasma membrane is compartmentalized and highly organized at the nanometer scale. Hence, a complete understanding of the precise conformation and activation mechanism of the BCR must take into account the organization of the B cell plasma membrane. We review here the recent literature on the nanoscale organization of the lymphocyte membrane and discuss how this new information influences our view of the conformational changes that the BCR undergoes during activation.

Keyword(s): B cell antigen receptor, B lymphocytes, BCR, membrane compartmentalization, nanocluster, protein islands, superresolution microscopy
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-042718-041704
2019-04-26
2025-04-30
Loading full text...

Full text loading...

/deliver/fulltext/immunol/37/1/annurev-immunol-042718-041704.html?itemId=/content/journals/10.1146/annurev-immunol-042718-041704&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Reth M, Wienands J 1997. Initiation and processing of signals from the B cell antigen receptor. Annu. Rev. Immunol. 15:453–79
     [Google Scholar]
  2. 2.  Attaf M, Legut M, Cole DK, Sewell AK 2015. The T cell antigen receptor: the Swiss army knife of the immune system. Clin. Exp. Immunol. 181:1–18
     [Google Scholar]
  3. 3.  Qian D, Weiss A 1997. T cell antigen receptor signal transduction. Curr. Opin. Cell Biol. 9:205–12
     [Google Scholar]
  4. 4.  Irving B, Weiss A 2014. A clue to antigen receptor tails. J. Immunol. 192:4013–14
     [Google Scholar]
  5. 5.  Reth M, Wienands J, Schamel WW 2000. An unsolved problem of the clonal selection theory and the model of an oligomeric B-cell antigen receptor. Immunol. Rev. 176:10–18
     [Google Scholar]
  6. 6.  Pierce SK, Liu W 2010. The tipping points in the initiation of B cell signalling: how small changes make big differences. Nat. Rev. Immunol. 10:767–77
     [Google Scholar]
  7. 7.  Niiro H, Clark EA 2002. Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2:945–56
     [Google Scholar]
  8. 8.  Gold MR 2002. To make antibodies or not: signaling by the B-cell antigen receptor. Trends Pharmacol. Sci. 23:316–24
     [Google Scholar]
  9. 9.  Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J 2004. B cell antigen receptor signaling 101. Mol. Immunol. 41:599–613
     [Google Scholar]
  10. 10.  Packard TA, Cambier JC 2013. B lymphocyte antigen receptor signaling: initiation, amplification, and regulation. F1000Prime Rep 5:40
     [Google Scholar]
  11. 11.  Kurosaki T 1999. Genetic analysis of B cell antigen receptor signaling. Annu. Rev. Immunol. 17:555–92
     [Google Scholar]
  12. 12.  Harwood NE, Batista FD 2010. Early events in B cell activation. Annu. Rev. Immunol. 28:185–210
     [Google Scholar]
  13. 13.  Mattila PK, Batista FD, Treanor B 2016. Dynamics of the actin cytoskeleton mediates receptor cross talk: an emerging concept in tuning receptor signaling. J. Cell Biol. 212:267–80
     [Google Scholar]
  14. 14.  Song W, Liu C, Upadhyaya A 2014. The pivotal position of the actin cytoskeleton in the initiation and regulation of B cell receptor activation. Biochim. Biophys. Acta 1838:569–78
     [Google Scholar]
  15. 15.  Tolar P 2017. Cytoskeletal control of B cell responses to antigens. Nat. Rev. Immunol. 17:621–34
     [Google Scholar]
  16. 16.  Kuokkanen E, Sustar V, Mattila PK 2015. Molecular control of B cell activation and immunological synapse formation. Traffic 16:311–26
     [Google Scholar]
  17. 17.  Yuseff MI, Pierobon P, Reversat A, Lennon-Dumenil AM 2013. How B cells capture, process and present antigens: a crucial role for cell polarity. Nat. Rev. Immunol. 13:475–86
     [Google Scholar]
  18. 18.  Hoogeboom R, Tolar P 2016. Molecular mechanisms of B cell antigen gathering and endocytosis. Curr. Top. Microbiol. Immunol. 393:45–63
     [Google Scholar]
  19. 19.  Mitrea DM, Kriwacki RW 2016. Phase separation in biology: functional organization of a higher order. Cell Commun. Signal. 14:1
     [Google Scholar]
  20. 20.  van Zanten TS, Cambi A, Garcia-Parajo MF 2010. A nanometer scale optical view on the compartmentalization of cell membranes. Biochim. Biophys. Acta 1798:777–87
     [Google Scholar]
  21. 21.  Maxfield FR 2002. Plasma membrane microdomains. Curr. Opin. Cell Biol. 14:483–87
     [Google Scholar]
  22. 22.  Harding AS, Hancock JF 2008. Using plasma membrane nanoclusters to build better signaling circuits. Trends Cell Biol 18:364–71
     [Google Scholar]
  23. 23.  Garcia-Parajo MF, Cambi A, Torreno-Pina JA, Thompson N, Jacobson K 2014. Nanoclustering as a dominant feature of plasma membrane organization. J. Cell Sci. 127:4995–5005
     [Google Scholar]
  24. 24.  Rothman JE 1994. Mechanisms of intracellular protein transport. Nature 372:55–63
     [Google Scholar]
  25. 25.  Singer SJ, Nicolson GL 1972. The fluid mosaic model of the structure of cell membranes. Science 175:720–31
     [Google Scholar]
  26. 26.  Schreiner GF, Unanue ER 1976. Calcium-sensitive modulation of Ig capping: evidence supporting a cytoplasmic control of ligand-receptor complexes. J. Exp. Med. 143:15–31
     [Google Scholar]
  27. 27.  Ma H, Yankee TM, Hu J, Asai DJ, Harrison ML, Geahlen RL 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. 166:1507–16
     [Google Scholar]
  28. 28.  Lillemeier BF, Mortelmaier MA, Forstner MB, Huppa JB, Groves JT, Davis MM 2010. TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nat. Immunol. 11:90–96
     [Google Scholar]
  29. 29.  Kumari S, Curado S, Mayya V, Dustin ML 2014. T cell antigen receptor activation and actin cytoskeleton remodeling. Biochim. Biophys. Acta 1838:546–56
     [Google Scholar]
  30. 30.  Dustin ML, Baldari CT 2017. The immune synapse: past, present, and future. Methods Mol. Biol. 1584:1–5
     [Google Scholar]
  31. 31.  Petit V, Thiery JP 2000. Focal adhesions: structure and dynamics. Biol. Cell 92:477–94
     [Google Scholar]
  32. 32.  Abbas AK, Ault KA, Karnovsky MJ, Unanue ER 1975. Non-random distribution of surface immunoglobulins on murine B lymphocytes. J. Immunol. 114:1197–204
     [Google Scholar]
  33. 33.  Sahl SJ, Hell SW, Jakobs S 2017. Fluorescence nanoscopy in cell biology. Nat. Rev. Mol. Cell Biol. 18:685–701
     [Google Scholar]
  34. 34.  Baddeley D, Bewersdorf J 2018. Biological insight from super-resolution microscopy: what we can learn from localization-based images. Annu. Rev. Biochem. 87:965–89
     [Google Scholar]
  35. 35.  Stone MB, Shelby SA, Veatch SL 2017. Super-resolution microscopy: shedding light on the cellular plasma membrane. Chem. Rev. 117:7457–77
     [Google Scholar]
  36. 36.  Sezgin E 2017. Super-resolution optical microscopy for studying membrane structure and dynamics. J. Phys. Condens. Matter 29:273001
     [Google Scholar]
  37. 37.  Stone MB, Veatch SL 2015. Steady-state cross-correlations for live two-colour super-resolution localization data sets. Nat. Commun. 6:7347
     [Google Scholar]
  38. 38.  Ashdown GW, Owen DM 2018. Spatio-temporal image correlation spectroscopy and super-resolution microscopy to quantify molecular dynamics in T cells. Methods 140–141:112–18
     [Google Scholar]
  39. 39.  Soderberg O, Leuchowius KJ, Gullberg M, Jarvius M, Weibrecht I et al. 2008. Characterizing proteins and their interactions in cells and tissues using the in situ proximity ligation assay. Methods 45:227–32
     [Google Scholar]
  40. 40.  Kläsener K, Yang J, Reth M 2018. Study B cell antigen receptor nano-scale organization by in situ Fab proximity ligation assay. Methods Mol. Biol. 1707:171–81
     [Google Scholar]
  41. 41.  Leavesley SJ, Rich TC 2016. Overcoming limitations of FRET measurements. Cytometry A 89:325–27
     [Google Scholar]
  42. 42.  Wilson BS, Pfeiffer JR, Oliver JM 2000. Observing FcεRI signaling from the inside of the mast cell membrane. J. Cell Biol. 149:1131–42
     [Google Scholar]
  43. 43.  Lillemeier BF, Pfeiffer JR, Surviladze Z, Wilson BS, Davis MM 2006. Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. PNAS 103:18992–97
     [Google Scholar]
  44. 44.  Mattila PK, Feest C, Depoil D, Treanor B, Montaner B et al. 2013. The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor-mediated signaling. Immunity 38:461–74
     [Google Scholar]
  45. 45.  Maity PC, Blount A, Jumaa H, Ronneberger O, Lillemeier BF, Reth M 2015. B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation. Sci. Signal. 8:ra93
     [Google Scholar]
  46. 46.  Wilson BS, Pfeiffer JR, Surviladze Z, Gaudet EA, Oliver JM 2001. High resolution mapping of mast cell membranes reveals primary and secondary domains of FcεRI and LAT. J. Cell Biol. 154:645–58
     [Google Scholar]
  47. 47.  Sherman E, Barr V, Manley S, Patterson G, Balagopalan L et al. 2011. Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. Immunity 35:705–20
     [Google Scholar]
  48. 48.  van Meer G, Simons K 1982. Viruses budding from either the apical or the basolateral plasma membrane domain of MDCK cells have unique phospholipid compositions. EMBO J 1:847–52
     [Google Scholar]
  49. 49.  Lingwood D, Simons K 2010. Lipid rafts as a membrane-organizing principle. Science 327:46–50
     [Google Scholar]
  50. 50.  Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S et al. 2006. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313:1642–45
     [Google Scholar]
  51. 51.  Owen DM, Rentero C, Rossy J, Magenau A, Williamson D et al. 2010. PALM imaging and cluster analysis of protein heterogeneity at the cell surface. J. Biophotonics 3:446–54
     [Google Scholar]
  52. 52.  Cambi A, Joosten B, Koopman M, de Lange F, Beeren I et al. 2006. Organization of the integrin LFA-1 in nanoclusters regulates its activity. Mol. Biol. Cell 17:4270–81
     [Google Scholar]
  53. 53.  Williamson DJ, Owen DM, Rossy J, Magenau A, Wehrmann M et al. 2011. Pre-existing clusters of the adaptor Lat do not participate in early T cell signaling events. Nat. Immunol. 12:655–62
     [Google Scholar]
  54. 54.  Yanez-Mo M, Barreiro O, Gordon-Alonso M, Sala-Valdes M, Sanchez-Madrid F 2009. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol 19:434–46
     [Google Scholar]
  55. 55.  Goswami D, Gowrishankar K, Bilgrami S, Ghosh S, Raghupathy R et al. 2008. Nanoclusters of GPI-anchored proteins are formed by cortical actin-driven activity. Cell 135:1085–97
     [Google Scholar]
  56. 56.  Lopes FB, Balint S, Valvo S, Felce JH, Hessel EM et al. 2017. Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages. J. Cell Biol. 216:1123–41
     [Google Scholar]
  57. 57.  Suzuki KG, Fujiwara TK, Sanematsu F, Iino R, Edidin M, Kusumi A 2007. GPI-anchored receptor clusters transiently recruit Lyn and Gα for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1. J. Cell Biol. 177:717–30
     [Google Scholar]
  58. 58.  Plowman SJ, Muncke C, Parton RG, Hancock JF 2005. H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton. PNAS 102:15500–5
     [Google Scholar]
  59. 59.  Remorino A, De Beco S, Cayrac F, Di Federico F, Cornilleau G et al. 2017. Gradients of Rac1 nano-clusters support spatial patterns of Rac1 signaling. Cell Rep 21:1922–35
     [Google Scholar]
  60. 60.  Liu W, Wang H, Xu C 2016. Antigen receptor nanoclusters: small units with big functions. Trends Immunol 37:680–89
     [Google Scholar]
  61. 61.  Harwood NE, Batista FD 2011. The cytoskeleton coordinates the early events of B-cell activation. Cold Spring Harb. Perspect. Biol. 3:a002360
     [Google Scholar]
  62. 62.  Bezanilla M, Gladfelter AS, Kovar DR, Lee WL 2015. Cytoskeletal dynamics: a view from the membrane. J. Cell Biol. 209:329–37
     [Google Scholar]
  63. 63.  Chhabra ES, Higgs HN 2007. The many faces of actin: matching assembly factors with cellular structures. Nat. Cell Biol. 9:1110–21
     [Google Scholar]
  64. 64.  Michelot A, Drubin DG 2011. Building distinct actin filament networks in a common cytoplasm. Curr. Biol. 21:R560–69
     [Google Scholar]
  65. 65.  Fritzsche M, Erlenkamper C, Moeendarbary E, Charras G, Kruse K 2016. Actin kinetics shapes cortical network structure and mechanics. Sci. Adv. 2:e1501337
     [Google Scholar]
  66. 66.  Bovellan M, Romeo Y, Biro M, Boden A, Chugh P et al. 2014. Cellular control of cortical actin nucleation. Curr. Biol. 24:1628–35
     [Google Scholar]
  67. 67.  Fritzsche M, Lewalle A, Duke T, Kruse K, Charras G 2013. Analysis of turnover dynamics of the submembranous actin cortex. Mol. Biol. Cell 24:757–67
     [Google Scholar]
  68. 68.  Morone N, Fujiwara T, Murase K, Kasai RS, Ike H et al. 2006. Three-dimensional reconstruction of the membrane skeleton at the plasma membrane interface by electron tomography. J. Cell Biol. 174:851–62
     [Google Scholar]
  69. 69.  Bretscher A, Chambers D, Nguyen R, Reczek D 2000. ERM-merlin and EBP50 protein families in plasma membrane organization and function. Annu. Rev. Cell Dev. Biol. 16:113–43
     [Google Scholar]
  70. 70.  Pore D, Gupta N 2015. The ezrin-radixin-moesin family of proteins in the regulation of B-cell immune response. Crit. Rev. Immunol. 35:15–31
     [Google Scholar]
  71. 71.  Fievet BT, Gautreau A, Roy C, Del Maestro L, Mangeat P et al. 2004. Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin. J. Cell Biol. 164:653–59
     [Google Scholar]
  72. 72.  Treanor B, Depoil D, Gonzalez-Granja A, Barral P, Weber M et al. 2010. The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor. Immunity 32:187–99
     [Google Scholar]
  73. 73.  Brown AC, Dobbie IM, Alakoskela JM, Davis I, Davis DM 2012. Super-resolution imaging of remodeled synaptic actin reveals different synergies between NK cell receptors and integrins. Blood 120:3729–40
     [Google Scholar]
  74. 74.  Kusumi A, Nakada C, Ritchie K, Murase K, Suzuki K et al. 2005. Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules. Annu. Rev. Biophys. Biomol. Struct. 34:351–78
     [Google Scholar]
  75. 75.  Kusumi A, Suzuki KG, Kasai RS, Ritchie K, Fujiwara TK 2011. Hierarchical mesoscale domain organization of the plasma membrane. Trends Biochem. Sci. 36:604–15
     [Google Scholar]
  76. 76.  Sherman E, Barr V, Samelson LE 2013. Super-resolution characterization of TCR-dependent signaling clusters. Immunol. Rev. 251:21–35
     [Google Scholar]
  77. 77.  Klammt C, Lillemeier BF 2012. How membrane structures control T cell signaling. Front. Immunol. 3:291
     [Google Scholar]
  78. 78.  Gutzeit C, Chen K, Cerutti A 2018. The enigmatic function of IgD: some answers at last. Eur. J. Immunol. 48:1101–13
     [Google Scholar]
  79. 79.  Ohta Y, Flajnik M 2006. IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates. PNAS 103:10723–28
     [Google Scholar]
  80. 80.  Roes J, Rajewsky K 1993. Immunoglobulin D (IgD)-deficient mice reveal an auxiliary receptor function for IgD in antigen-mediated recruitment of B cells. J. Exp. Med. 177:45–55
     [Google Scholar]
  81. 81.  Sabouri Z, Perotti S, Spierings E, Humburg P, Yabas M et al. 2016. IgD attenuates the IgM-induced anergy response in transitional and mature B cells. Nat. Commun. 7:13381
     [Google Scholar]
  82. 82.  Noviski M, Mueller JL, Satterthwaite A, Garrett-Sinha LA, Brombacher F, Zikherman J 2018. IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate. eLife 7:e35074
     [Google Scholar]
  83. 83.  Githaka JM, Vega AR, Baird MA, Davidson MW, Jaqaman K, Touret N 2016. Ligand-induced growth and compaction of CD36 nanoclusters enriched in Fyn induces Fyn signaling. J. Cell Sci. 129:4175–89
     [Google Scholar]
  84. 84.  Balint S, Lopes FB, Davis DM 2018. A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner. Sci. Signal. 11:eaal3606
     [Google Scholar]
  85. 85.  Lee J, Sengupta P, Brzostowski J, Lippincott-Schwartz J, Pierce SK 2017. The nanoscale spatial organization of B-cell receptors on immunoglobulin M- and G-expressing human B-cells. Mol. Biol. Cell 28:511–23
     [Google Scholar]
  86. 86.  Kläsener K, Maity PC, Hobeika E, Yang J, Reth M 2014. B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk. eLife 3:e02069
     [Google Scholar]
  87. 87.  Cheng PC, Cherukuri A, Dykstra M, Malapati S, Sproul T et al. 2001. Floating the raft hypothesis: the roles of lipid rafts in B cell antigen receptor function. Semin. Immunol. 13:107–14
     [Google Scholar]
  88. 88.  Gupta N, DeFranco AL 2003. Visualizing lipid raft dynamics and early signaling events during antigen receptor-mediated B-lymphocyte activation. Mol. Biol. Cell 14:432–44
     [Google Scholar]
  89. 89.  Maity PC, Yang J, Klaesener K, Reth M 2015. The nanoscale organization of the B lymphocyte membrane. Biochim. Biophys. Acta 1853:830–40
     [Google Scholar]
  90. 90.  Gupta N, Wollscheid B, Watts JD, Scheer B, Aebersold R, DeFranco AL 2006. Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor-mediated lipid raft dynamics. Nat. Immunol. 7:625–33
     [Google Scholar]
  91. 91.  Vences-Catalan F, Rajapaksa R, Levy S, Santos-Argumedo L 2012. The CD19/CD81 complex physically interacts with CD38 but is not required to induce proliferation in mouse B lymphocytes. Immunology 137:48–55
     [Google Scholar]
  92. 92.  Limon JJ, Fruman DA 2012. Akt and mTOR in B cell activation and differentiation. Front. Immunol. 3:228
     [Google Scholar]
  93. 93.  Schweighoffer E, Tybulewicz VL 2018. Signalling for B cell survival. Curr. Opin. Cell Biol. 51:8–14
     [Google Scholar]
  94. 94.  Keppler SJ, Gasparrini F, Burbage M, Aggarwal S, Frederico B et al. 2015. Wiskott-Aldrich syndrome interacting protein deficiency uncovers the role of the co-receptor CD19 as a generic hub for PI3 kinase signaling in B cells. Immunity 43:660–73
     [Google Scholar]
  95. 95.  Kremer KN, Humphreys TD, Kumar A, Qian NX, Hedin KE 2003. Distinct role of ZAP-70 and Src homology 2 domain-containing leukocyte protein of 76 kDa in the prolonged activation of extracellular signal-regulated protein kinase by the stromal cell-derived factor-1 alpha/CXCL12 chemokine. J. Immunol. 171:360–67
     [Google Scholar]
  96. 96.  Kumar A, Humphreys TD, Kremer KN, Bramati PS, Bradfield L et al. 2006. CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity 25:213–24
     [Google Scholar]
  97. 97.  Becker M, Hobeika E, Jumaa H, Reth M, Maity PC 2017. CXCR4 signaling and function require the expression of the IgD-class B-cell antigen receptor. PNAS 114:5231–36
     [Google Scholar]
  98. 98.  Reth MG 2018. The nanoscale organization of the BCR and the B cell membrane Presented at Keystone Symposium on Molecular and Cellular Biology, Dresden, Ger., Jun 17–21
     [Google Scholar]
  99. 99.  Cheng PC, Dykstra ML, Mitchell RN, Pierce SK 1999. A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J. Exp. Med. 190:1549–60
     [Google Scholar]
  100. 100.  Gasparrini F, Feest C, Bruckbauer A, Mattila PK, Muller J et al. 2016. Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling. EMBO J 35:258–80
     [Google Scholar]
  101. 101.  Cornall RJ, Goodnow CC, Cyster JG 1999. Regulation of B cell antigen receptor signaling by the Lyn/CD22/SHP1 pathway. Curr. Top. Microbiol. Immunol. 244:57–68
     [Google Scholar]
  102. 102.  Coughlin S, Noviski M, Mueller JL, Chuwonpad A, Raschke WC et al. 2015. An extracatalytic function of CD45 in B cells is mediated by CD22. PNAS 112:E6515–24
     [Google Scholar]
  103. 103.  Depoil D, Dustin ML 2016. Agile CD22 nanoclusters run rings around fenced BCR. EMBO J 35:237–38
     [Google Scholar]
  104. 104.  Rees JS, Li XW, Perrett S, Lilley KS, Jackson AP 2015. Protein neighbors and proximity proteomics. Mol. Cell Proteom. 14:2848–56
     [Google Scholar]
  105. 105.  Han S, Li J, Ting AY 2018. Proximity labeling: spatially resolved proteomic mapping for neurobiology. Curr. Opin. Neurobiol. 50:17–23
     [Google Scholar]
  106. 106.  Anderson RG, Jacobson K 2002. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296:1821–25
     [Google Scholar]
  107. 107.  Gowrishankar K, Ghosh S, Saha S, Rumamol C, Mayor S, Rao M 2012. Active remodeling of cortical actin regulates spatiotemporal organization of cell surface molecules. Cell 149:1353–67
     [Google Scholar]
  108. 108.  Brugger B, Sandhoff R, Wegehingel S, Gorgas K, Malsam J et al. 2000. Evidence for segregation of sphingomyelin and cholesterol during formation of COPI-coated vesicles. J. Cell Biol. 151:507–18
     [Google Scholar]
  109. 109.  Gkantiragas I, Brugger B, Stuven E, Kaloyanova D, Li XY et al. 2001. Sphingomyelin-enriched microdomains at the Golgi complex. Mol. Biol. Cell 12:1819–33
     [Google Scholar]
  110. 110.  Duran JM, Campelo F, van Galen J, Sachsenheimer T, Sot J et al. 2012. Sphingomyelin organization is required for vesicle biogenesis at the Golgi complex. EMBO J 31:4535–46
     [Google Scholar]
  111. 111.  Barlowe C, Helenius A 2016. Cargo capture and bulk flow in the early secretory pathway. Annu. Rev. Cell Dev. Biol. 32:197–222
     [Google Scholar]
  112. 112.  Borgese N 2016. Getting membrane proteins on and off the shuttle bus between the endoplasmic reticulum and the Golgi complex. J. Cell Sci. 129:1537–45
     [Google Scholar]
  113. 113.  Bonello G, Blanchard N, Montoya MC, Aguado E, Langlet C et al. 2004. Dynamic recruitment of the adaptor protein LAT: LAT exists in two distinct intracellular pools and controls its own recruitment. J. Cell Sci. 117:1009–16
     [Google Scholar]
  114. 114.  Rocha-Perugini V, Sanchez-Madrid F, Martinez Del Hoyo G 2015. Function and dynamics of tetraspanins during antigen recognition and immunological synapse formation. Front. Immunol. 6:653
     [Google Scholar]
  115. 115.  Zuidscherwoude M, Gottfert F, Dunlock VM, Figdor CG, van den Bogaart G, van Spriel AB 2015. The tetraspanin web revisited by super-resolution microscopy. Sci. Rep. 5:12201
     [Google Scholar]
  116. 116.  Sanyal M, Fernandez R, Levy S 2009. Enhanced B cell activation in the absence of CD81. Int. Immunol. 21:1225–37
     [Google Scholar]
  117. 117.  Kovtun O, Tillu VA, Ariotti N, Parton RG, Collins BM 2015. Cavin family proteins and the assembly of caveolae. J. Cell Sci. 128:1269–78
     [Google Scholar]
  118. 118.  Thomsen P, Roepstorff K, Stahlhut M, van Deurs B 2002. Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking. Mol. Biol. Cell 13:238–50
     [Google Scholar]
  119. 119.  Minguet S, Kläsener K, Schaffer AM, Fiala GJ, Osteso-Ibanez T et al. 2017. Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance. Nat. Immunol. 18:1150–59
     [Google Scholar]
  120. 120.  Metzger H 1992. Transmembrane signaling: the joy of aggregation. J. Immunol. 149:1477–87
     [Google Scholar]
  121. 121.  Treanor B 2012. B-cell receptor: from resting state to activate. Immunology 136:21–27
     [Google Scholar]
  122. 122.  Tolar P, Pierce SK 2010. A conformation-induced oligomerization model for B cell receptor microclustering and signaling. Curr. Top. Microbiol. Immunol. 340:155–69
     [Google Scholar]
  123. 123.  Schamel WW, Reth M 2000. Monomeric and oligomeric complexes of the B cell antigen receptor. Immunity 13:5–14
     [Google Scholar]
  124. 124.  Schlessinger J 2003. Signal transduction: autoinhibition control. Science 300:750–52
     [Google Scholar]
  125. 125.  Sicheri F, Kuriyan J 1997. Structures of Src-family tyrosine kinases. Curr. Opin. Struct. Biol. 7:777–85
     [Google Scholar]
  126. 126.  Goksoy E, Ma YQ, Wang X, Kong X, Perera D et al. 2008. Structural basis for the autoinhibition of talin in regulating integrin activation. Mol. Cell 31:124–33
     [Google Scholar]
  127. 127.  Desai DM, Sap J, Schlessinger J, Weiss A 1993. Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase. Cell 73:541–54
     [Google Scholar]
  128. 128.  Majeti R, Bilwes AM, Noel JP, Hunter T, Weiss A 1998. Dimerization-induced inhibition of receptor protein tyrosine phosphatase function through an inhibitory wedge. Science 279:88–91
     [Google Scholar]
  129. 129.  Yang J, Reth M 2010. The dissociation activation model of B cell antigen receptor triggering. FEBS Lett 584:4872–77
     [Google Scholar]
  130. 130.  Yang J, Reth M 2010. Oligomeric organization of the B-cell antigen receptor on resting cells. Nature 467:465–69
     [Google Scholar]
  131. 131.  Kim YM, Pan JY, Korbel GA, Peperzak V, Boes M, Ploegh HL 2006. Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation. PNAS 103:3327–32
     [Google Scholar]
  132. 132.  Avalos AM, Bilate AM, Witte MD, Tai AK, He J et al. 2014. Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells. J. Exp. Med. 211:365–79
     [Google Scholar]
  133. 133.  Mukherjee S, Zhu J, Zikherman J, Parameswaran R, Kadlecek TA et al. 2013. Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases. Sci. Signal. 6: ra1
    [Google Scholar]
  134. 134.  Volkmann C, Brings N, Becker M, Hobeika E, Yang J, Reth M 2016. Molecular requirements of the B-cell antigen receptor for sensing monovalent antigens. EMBO J 35:2371–81
     [Google Scholar]
  135. 135.  Stepanek O, Draber P, Drobek A, Horejsi V, Brdicka T 2013. Nonredundant roles of Src-family kinases and Syk in the initiation of B-cell antigen receptor signaling. J. Immunol. 190:1807–18
     [Google Scholar]
  136. 136.  Sela-Culang I, Alon S, Ofran Y 2012. A systematic comparison of free and bound antibodies reveals binding-related conformational changes. J. Immunol. 189:4890–99
     [Google Scholar]
  137. 137.  Natkanski E, Lee WY, Mistry B, Casal A, Molloy JE, Tolar P 2013. B cells use mechanical energy to discriminate antigen affinities. Science 340:1587–90
     [Google Scholar]
  138. 138.  Liu QH, Liu X, Wen Z, Hondowicz B, King L et al. 2005. Distinct calcium channels regulate responses of primary B lymphocytes to B cell receptor engagement and mechanical stimuli. J. Immunol. 174:68–79
     [Google Scholar]
  139. 139.  Wan Z, Chen X, Chen H, Ji Q, Chen Y et al. 2015. The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold. eLife 4:e06925
     [Google Scholar]
  140. 140.  Ubelhart R, Hug E, Bach MP, Wossning T, Duhren-von Minden M et al. 2015. Responsiveness of B cells is regulated by the hinge region of IgD. Nat. Immunol. 16:534–43
     [Google Scholar]
  141. 141.  de Castro RO 2011. Regulation and function of syk tyrosine kinase in mast cell signaling and beyond. J. Signal. Transduct. 2011:507291
     [Google Scholar]
  142. 142.  Rolli V, Gallwitz M, Wossning T, Flemming A, Schamel WW et al. 2002. Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol. Cell 10:1057–69
     [Google Scholar]
  143. 143.  Schamel WW, Alarcon B, Hofer T, Minguet S 2017. The allostery model of TCR regulation. J. Immunol. 198:47–52
     [Google Scholar]
  144. 144.  Martin-Blanco N, Blanco R, Alda-Catalinas C, Bovolenta ER, Oeste CL et al. 2018. A window of opportunity for cooperativity in the T cell receptor. Nat. Commun. 9:2618
     [Google Scholar]
  145. 145.  Balagopalan L, Kortum RL, Coussens NP, Barr VA, Samelson LE 2015. The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters. J. Biol. Chem. 290:26422–29
     [Google Scholar]
  146. 146.  Freeman SA, Jaumouille V, Choi K, Hsu BE, Wong HS et al. 2015. Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor. Nat. Commun. 6:6168
     [Google Scholar]
  147. 147.  Freeman SA, Lei V, Dang-Lawson M, Mizuno K, Roskelley CD, Gold MR 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. 187:5887–900
     [Google Scholar]
  148. 148.  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. 208:1055–68
     [Google Scholar]
  149. 149.  Pore D, Parameswaran N, Matsui K, Stone MB, Saotome I et al. 2013. Ezrin tunes the magnitude of humoral immunity. J. Immunol. 191:4048–58
     [Google Scholar]
  150. 150.  Liu C, Miller H, Orlowski G, Hang H, Upadhyaya A, Song W 2012. Actin reorganization is required for the formation of polarized B cell receptor signalosomes in response to both soluble and membrane-associated antigens. J. Immunol. 188:3237–46
     [Google Scholar]
  151. 151.  Ohashi K 2015. Roles of cofilin in development and its mechanisms of regulation. Dev. Growth Differ. 57:275–90
     [Google Scholar]
  152. 152.  Mizuno K 2013. Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation. Cell Signal 25:457–69
     [Google Scholar]
  153. 153.  Bravo-Cordero JJ, Magalhaes MA, Eddy RJ, Hodgson L, Condeelis J 2013. Functions of cofilin in cell locomotion and invasion. Nat. Rev. Mol. Cell Biol. 14:405–15
     [Google Scholar]
  154. 154.  Viswanatha R, Ohouo PY, Smolka MB, Bretscher A 2012. Local phosphocycling mediated by LOK/SLK restricts ezrin function to the apical aspect of epithelial cells. J. Cell Biol. 199:969–84
     [Google Scholar]
  155. 155.  Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S 2009. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. PNAS 106:4707–12
     [Google Scholar]
  156. 156.  Stone MB, Shelby SA, Nunez MF, Wisser K, Veatch SL 2017. Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes. eLife 6:e19891
     [Google Scholar]
  157. 157.  Brdicka T, Pavlistova D, Leo A, Bruyns E, Korinek V et al. 2000. Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J. Exp. Med. 191:1591–604
     [Google Scholar]
  158. 158.  Fujimoto M, Poe JC, Hasegawa M, Tedder TF 2000. CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Immunol. Res. 22:281–98
     [Google Scholar]
  159. 159.  Shelby SA, Veatch SL, Holowka DA, Baird BA 2016. Functional nanoscale coupling of Lyn kinase with IgE-FcεRI is restricted by the actin cytoskeleton in early antigen-stimulated signaling. Mol. Biol. Cell 27:3645–58
     [Google Scholar]
  160. 160.  Pao LI, Famiglietti SJ, Cambier JC 1998. Asymmetrical phosphorylation and function of immunoreceptor tyrosine-based activation motif tyrosines in B cell antigen receptor signal transduction. J. Immunol. 160:3305–14
     [Google Scholar]
  161. 161.  Saijo K, Schmedt C, Su IH, Karasuyama H, Lowell CA et al. 2003. Essential role of Src-family protein tyrosine kinases in NF-κB activation during B cell development. Nat. Immunol. 4:274–79
     [Google Scholar]
  162. 162.  So L, Fruman DA 2012. PI3K signalling in B- and T-lymphocytes: new developments and therapeutic advances. Biochem. J. 442:465–81
     [Google Scholar]
  163. 163.  Newman R, Turner M 2015. The role of p110δ in the development and activation of B lymphocytes. Adv. Exp. Med. Biol. 850:119–35
     [Google Scholar]
  164. 164.  Arana E, Harwood NE, Batista FD 2008. Regulation of integrin activation through the B-cell receptor. J. Cell Sci. 121:2279–86
     [Google Scholar]
  165. 165.  Arana E, Vehlow A, Harwood NE, Vigorito E, Henderson R et al. 2008. Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation. Immunity 28:88–99
     [Google Scholar]
  166. 166.  Doody GM, Bell SE, Vigorito E, Clayton E, McAdam S et al. 2001. Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation. Nat. Immunol. 2:542–47
     [Google Scholar]
  167. 167.  Justement LB, Campbell KS, Chien NC, Cambier JC 1991. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. Science 252:1839–42
     [Google Scholar]
  168. 168.  Cox DBT, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ et al. 2017. RNA editing with CRISPR-Cas13. Science 358:1019–27
     [Google Scholar]
/content/journals/10.1146/annurev-immunol-042718-041704
Loading
Antigen Receptor Function in the Context of the Nanoscale Organization of the B Cell Membrane
Annual Review of Immunology 37, 97 (2019); https://doi.org/10.1146/annurev-immunol-042718-041704
/content/journals/10.1146/annurev-immunol-042718-041704
/content/journals/10.1146/annurev-immunol-042718-041704
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error