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Epithelial Transcytosis of Immunoglobulins

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Abstract

Transcytosis plays a central role in theimmunological functions of epithelia, including thesampling of antigens that enter the body via thedigestive, respiratory and urogenital tracts and theirpresentation to underlying lymphoid tissues, the secretionof specific immunoglobulins required for the immuneprotection of mucosal surfaces and the transfer ofmaternal immunoglobulins to the fetus or newborn,providing the latter with passive immunity for the firstweeks of independent life.

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References

  1. M. R. Neutra, E. Pringault, and J. P. Kraehenbuhl (1996). Antigen sampling across epithelial barriers and induction of mucosal immune responses. Ann. Rev. Immunol. 14: 275-300.

    Google Scholar 

  2. B. L. Kelsall and W. Strober (1997). Dendritic cells of the gastrointestinal tract. Springer Semin. Immunopathol. 18: 409-420.

    Google Scholar 

  3. Y. J. Liu, G. D. Johnson, J. Gordon, and I. C. MacLennan (1992). Germinal centres in T-cell-dependent antibody responses. Immunol. Today 13: 17-21.

    Google Scholar 

  4. W. Strober and O. R. Ehrhardt (1994). Regualtion of IgA B cell development. In J. M. P. L. Ogra, M. L. Lamm, W. Strober, J. R. McGhee, and J. Bienenstock (eds.), Handbook of Mucosal Immunology Academic Press, pp.159-176.

  5. M. Quiding-Jabrink, I. Nordstrom, G. Granstrom, A. Kilander, M. Jertborn, E. C. Butcher, A. I. Lazarovits, J. Holmgren, and C. Czerkinsky (1997). Differential expression of tissue-specific adhesion molecules on human circulating antibody-forming cells after systemic, enteric, and nasal immunizations. A molecular basis for the compartmentalization of effector B cell responses. J. Clin. Invest. 99: 1281-1286.

    Google Scholar 

  6. C. Berlin, R. F. Bargatze, J. J. Campbell, U. H. von Andrian, M. C. Szabo, S. R. Hasslen, R. D. Nelson, E. L. Berg, S. L. Erlandsen, and E. C. Butcher (1995). Alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80: 413-422.

    Google Scholar 

  7. P. Weisz-Carrington, M. E. Roux, M. McWilliams, J. M. Phillips-Quagliata, and M. E. Lamm (1978). Hormonal induction of the secretory immune system in the mammary gland. Proc. Natl. Acad. Sci. U.S.A. 75: 2928-2932.

    Google Scholar 

  8. S. J. Czinn and M. E. Lamm (1986). Selective chemotaxis of subsets of B lymphocytes from gut-associated lymphoid tissue and its implications for the recruitment of mucosal plasma cells. J. Immunol. 136: 3607-3611.

    Google Scholar 

  9. L. Osborn, C. Hession, R. Tizard, C. Vassallo, S. Luhowskyj, G. Chi-Rosso, and R. Lobb (1989). Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59: 1203-1211.

    Google Scholar 

  10. E. C. Butcher and L. J. Picker (1996). Lymphocyte homing and homeostasis. Science 272: 60-66.

    Google Scholar 

  11. R. Forster, A. E. Mattis, E. Kremmer, E. Wolf, G. Brem, and M. Lipp (1996). A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 87: 1037-1047.

    Google Scholar 

  12. A. J. Ramsay, A. J. Husband, I. A. Ramshaw, S. Bao, K. I. Matthaei, G. Koehler, and M. Kopf (1994). The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science 264: 561-563.

    Google Scholar 

  13. A. K. Bromander, L. Ekman, M. Kopf, J. G. Nedrud, and N. Y. Lycke (1996). IL-6-deficient mice exhibit normal mucosal IgA responses to local immunizations and Helicobacter felis infection. J. Immunol. 156: 4290-4297.

    Google Scholar 

  14. K. Bjerke and P. Brandtzaeg (1990). Terminally differentiated human intestinal B cells. J chain expression of IgA and IgG subclass-producing immunocytes in the distal ileum compared with mesenteric and peripheral lymph nodes. Clin. Exp. Immunol. 82: 411-415.

    Google Scholar 

  15. K. E. Mostov (1994). Transepithelial transport of immunoglobulins. Ann. Rev. Immunol. 12: 63-84.

    Google Scholar 

  16. K. E. Mostov, Y. Altschuler, S. J. Chapin, C. Enrich, S. H. Low, F. Luton, J. Richman-Eisenstat, K. L. Singer, K. Tang, and T. Weimbs (1995). Regulation of protein traffic in polarized epithelial cells: The polymeric immunoglobulin receptor model. Cold Spring Harbor Symp. Quant. Biol. 60: 775-781.

    Google Scholar 

  17. G. J. Hughes, S. Frutiger, L. A. Savoy, A. J. Reason, H. R. Morris, and J. C. Jaton (1997). Human free secretory component is composed of the first 585 amino acid residues of the polymeric immunoglobulin receptor. FEBS Lett. 410: 443-446.

    Google Scholar 

  18. R. S. Coyne, M. Siebrecht, M. C. Peitsch, and J. E. Casanova (1994). Mutational analysis of polymeric immunoglobulin receptor ligand interactions—evidence for the involvement of multiple complementarity determining region (CDR)-like loops in receptor domain i. J. Biol. Chem. 269: 31620-31625.

    Google Scholar 

  19. B. Corthesy, M. Kaufmann, A. Phalipon, M. Peitsch, M. R. Neutra, and J. P. Kraehenbuhl (1996). A pathogen-specific epitope inserted into recombinant secretory immunoglobulin A is immunogenic by the oral route. J. Biol. Chem. 271: 33670-33677.

    Google Scholar 

  20. J. Mestecky and J. R. McGhee (1987). Immunoglobulin A (IgA): Molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv. Immunol. 40: 153-245.

    Google Scholar 

  21. M. A. Kerr (1990). The structure and function of human IgA. Biochem. J. 271: 285-296.

    Google Scholar 

  22. A. E. Wold, C. Motas, C. Svanborg, and J. Mestecky (1994). Lectin receptors on IgA isotypes. Scand. J. Immunol. 39: 195-201.

    Google Scholar 

  23. A. G. Plaut (1988). Production and isolation of neissereal IgA proteases. Meth. Enzymol. 165: 117-120.

    Google Scholar 

  24. G. Donadel, A. Calabro, G. Sigounas, V. C. Hascall, A. L. Notkins, and N. Harindranath (1994). Human polyreactive and monoreactive antibodies: Effect of glycosylation on antigen binding. Glycobiology 4: 491-496.

    Google Scholar 

  25. B. A. Hendrickson, D. A. Conner, D. J. Ladd, D. Kendall, J. E. Casanova, B. Corthesy, E. E. Max, M. R. Neutra, C. E. Seidman, and J. G. Seidman (1995). Altered hepatic transport of immunoglobulin A in mice lacking the J chain. J. Exp. Med. 182: 1905-1911.

    Google Scholar 

  26. B. A. Hendrickson, L. Rindisbacher, B. Corthesy, D. Kendall, D. A. Waltz, M. R. Neutra, and J. G. Seidman (1996). Lack of association of secretory component with IgA in J chain-deficient mice. J. Immunol. 157: 750-754.

    Google Scholar 

  27. L. Rindisbacher, S. Cottet, R. Wittek, J. P. Kraehenbuhl, and B. Corthesy (1995). Production of human secretory component with dimeric IgA binding capacity using viral expression systems. J. Biol. Chem. 270: 14220-14228.

    Google Scholar 

  28. R. P. Hirt, G. J. Hughes, S. Frutiger, P. Michetti, C. Perregaux, O. Poulaingodefroy, N. Jeanguenat, M. R. Neutra, and J. P. Kraehenbuhl (1993). Transcytosis of the polymeric ig receptor requires phosphorylation of serine-664 in the absence but not the presence of dimeric IgA. Cell 74: 245-255.

    Google Scholar 

  29. K. L. Singer and K. E. Mostov (1998). Dimerization of the polymeric immunoglobulin receptor controls its transcytotic trafficking. Mol. Biol. Cell. (in press).

  30. C. M. Tamer, M. E. Lamm, J. K. Robinson, J. F. Piskurich, and C. S. Kaetzel (1995). Comparative studies of transcytosis and assembly of secretory IgA in Madin-Darby canine kidney cells expressing human polymeric Ig receptor. J. Immunol. 155: 707-714.

    Google Scholar 

  31. E. Lullau, S. Heyse, H. Vogel, I. Marison, U. von Stockar, J. P. Kraehenbuhl, and B. Corthesy (1996). Antigen binding properties of purified immunoglobulin A and reconstituted secretory immunoglobulin A antibodies. J. Biol. Chem. 271: 16300-16309.

    Google Scholar 

  32. C. S. Kaetzel, V. J. Blanch, P. M. Hempen, K. M. Phillips, J. F. Piskurich, and K. R. Youngman (1997). The polymeric immunoglobulin receptor—structure and synthesis. Biochem. Soc. Trans. 25: 475-480.

    Google Scholar 

  33. R. H. Prabhala and C. R. Wira (1991). Cytokine regulation of the mucosal immune system: In vivo stimulation by interferon-gamma of secretory component and immunoglobulin A in uterine secretions and proliferation of lymphocytes from spleen. Endocrinology 129: 2915-2923.

    Google Scholar 

  34. G. M. Denning (1996). IL-4 and IFN-gamma synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. Role of protein tyrosine kinases. J. Immunol. 156: 4807-4814.

    Google Scholar 

  35. R. Rosato, H. Jammes, L. Belair, C. Puissant, J. P. Kraehenbuhl, and J. Djiane (1995). Polymeric-Ig receptor gene expression in rabbit mammary gland during pregnancy and lactation: Evolution and hormonal regulation. Mol. Cell. Endocrinol. 110: 81-87.

    Google Scholar 

  36. P. Keller and K. Simons (1997). Post-Golgi biosynthetic trafficking. J. Cell Sci. 110: 3001-3009.

    Google Scholar 

  37. L. Saucan and G. E. Palade (1994). Membrane and secretory proteins are transported from the Golgi complex to the sinusoidal plasmalemma of hepatocytes by distinct vesicular carriers. J. Cell Biol. 125: 733-741.

    Google Scholar 

  38. S. L. Schmid (1997). Clathrin-coated vesicle formation and protein sorting—an integrated process. Ann. Rev. Biochem. 66: 511-548.

    Google Scholar 

  39. B. Aroeti and K. E. Mostov (1994). Polarized sorting of the polymeric immunoglobulin receptor in the exocytotic and endocytotic pathways is controlled by the same amino acids. EMBO J. 13: 2297-2304.

    Google Scholar 

  40. K. Simons and E. Ikonen (1997). Functional rafts in cell membranes. Nature 387: 569-572.

    Google Scholar 

  41. A. Gut, F. Kappeler, N. Hyka, B. M. S. H.-P. Hauri, and K. Matter (1998). Carbohydrate-mediated Golgi to cell surface transport an apical targeting of membrane proteins. EMBO J. (in press.)

  42. G. Apodaca, M. H. Cardone, S. W. Whiteheart, B. R. Dasgupta, and K. E. Mostov (1996). Reconstitution of transcytosis in SLO-permeabilized MDCK cells—existence of an NSF-dependent fusion mechanism with the apical surface of MDCK cells. EMBO J. 15: 1471-1481.

    Google Scholar 

  43. G. Apodaca, L. A. Katz, and K. E. Mostov (1994). Receptormediated transcytosis of IgA in MDCK cells is via apical recycling endosomes. J. Cell Biol. 125: 67-86.

    Google Scholar 

  44. M. Barroso and E. S. Sztul (1994). Basolateral to apical transcytosis in polarized cells is indirect and involves BFA and trimeric-G protein sensitive passage through the apical endosome. J. Cell Biol. 124: 83-100.

    Google Scholar 

  45. G. Odorizzi, A. Pearse, D. Domingo, I. S. Trowbridge, and C. R. Hopkins (1996). Apical and basolateral endosomes of MDCK cells are interconnected and contain a polarized sorting mechanism. J. Cell Biol. 135: 139-152.

    Google Scholar 

  46. J. Gruenberg and F. R. Maxfield (1995). Membrane transport in the endocytic pathway. Curr. Opin. Cell Biol. 7: 552-563.

    Google Scholar 

  47. I. Mellman (1996). Endocytosis and molecular sorting. Ann. Rev. Cell Dev. Biol. 12: 575-625.

    Google Scholar 

  48. S. J. Chapin, C. Enrich, B. Aroeti, R. J. Havel, and K. E. Mostov (1996). Calmodulin binds to the basolateral targeting signal of the polymeric immunoglobulin receptor. J. Biol. Chem. 271: 1336-1342.

    Google Scholar 

  49. W. Hunziker (1994). The calmodulin antagonist W-7 affects transcytosis, lysosomal transport, and recycling but not endocytosis. J. Biol. Chem. 269: 29003-29009.

    Google Scholar 

  50. G. Apodaca, C. Enrich, and K. E. Mostov (1994). The calmodulin antagonist, W-13, alters transcytosis, recycling, and the morphology of the endocytic pathway in Madin-Darby canine kidney cells. J. Biol. Chem. 269: 19005-19013.

    Google Scholar 

  51. C. J. Maples, W. G. Ruiz, and G. Apodaca (1997). Both microtubules and actin filaments are required for efficient postendocytotic traffic of the polymeric immunoglobulin receptor in polarized Madin-Darby canine kidney cells. J. Biol. Chem. 272: 6741-6751.

    Google Scholar 

  52. W. X. Song, M. Bomsel, J. Casanova, J. P. Vaerman, and K. Mostov (1994). Stimulation of transcytosis of the polymeric immunoglobulin receptor by dimeric IgA. Proc. Natl. Acad. Sci. U.S.A. 91: 163-166.

    Google Scholar 

  53. D. Giffroy, A. Langendries, M. Maurice, F. Daniel, B. Lardeux, and J.-P. Vaerman (1998). In vivo stimulation of polymeric Ig receptor-transcytosis by circulating polymeric IgA in rat liver. Int. Immunol. 10: 347-352.

    Google Scholar 

  54. W. Song, G. Apodaca, and K. Mostov (1994). Transcytosis of the polymeric immunoglobulin receptor is regulated in multiple intracellular compartments. J. Biol. Chem. 269: 29474-29480.

    Google Scholar 

  55. M. H. Cardone, B. L. Smith, P. A. Mennitt, D. Mochly-Rosen, R. B. Silver, and K. E. Mostov (1996). Signal transduction by the polymeric immunoglobulin receptor suggests a role in regulation of receptor transcytosis. J. Cell Biol. 133: 997-1005.

    Google Scholar 

  56. F. W. R. Brambell (1970). The Transmission of Passive Immunity from Mother to Young North-Holland Publishing Co., Amsterdam, p. 385.

    Google Scholar 

  57. N. A. Bright, C. D. Ockleford, and M. Anwar (1994). Ontogeny and distribution of Fc gamma receptors in the human placenta—transport or immune surveillance. J. Anat. 184: 297-308.

    Google Scholar 

  58. M. Daeron (1997). Fc receptor biology. Ann. Rev. Immunol. 15: 203-234.

    Google Scholar 

  59. M. Raghavan and P. J. Bjorkman (1996). Fc receptors and their interactions with immunoglobulins. Ann. Rev. Cell Dev. Biol. 12: 181-220.

    Google Scholar 

  60. F. Saji, M. Koyama, and N. Matsuzaki (1994). Human placental Fc receptors. Placenta 15: 453-466.

    Google Scholar 

  61. N. E. Simister and K. E. Mostov (1989). An Fc receptor structurally related to MHC class I antigens. Nature 337: 184-187.

    Google Scholar 

  62. E. Kandil, M. Egashira, O. Miyosi, N. Niikawa, T. Ishibashi, and M. Kasahara (1996). The human gene encoding the heavy chain of the major histocompatibility complex class 1-like Fc receptor (FcRn) maps to 19q13.3. Cytogen. Cell Gene 73: 97-98.

    Google Scholar 

  63. V. Ghetie and E. S. Ward (1997). FcRn: The MHC class I-related receptor that is more than an IgG transporter. Immunol. Today 18: 592-598.

    Google Scholar 

  64. D. E. Vaughn and P. J. Bjorkman (1997). High-affinity binding of the neonatal Fc receptor to its IgG ligand requires receptor immobilization. Biochemistry 36: 9374-9380.

    Google Scholar 

  65. N. E. Simister and A. Rees (1985). Isolation and characterization of an Fc receptor from neonatal rat small intestine. Eur. J. Immunol. 15: 733-738.

    Google Scholar 

  66. N. E. Simister, E. J. Israel, J. C. Ahouse, and C. M. Story (1997). New functions of the MHC class I-related Fc receptor, FcRn. Biochem. Soc. Trans. 25: 481-486.

    Google Scholar 

  67. M. G. Martin, S. V. Wu, and J. H. Walsh (1997). Ontogenetic development and distribution of antibody transport and Fc receptor mRNA expression in rat intestine. Digest. Diseases Sci. 42: 1062-1069.

    Google Scholar 

  68. E. J. Israel, V. K. Patel, S. F. Taylor, A. Marshakrothstein, and N. Simister (1995). Requirement for a beta(2)-microglobulinassociated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice. J. Immunol. 154: 6246-6251.

    Google Scholar 

  69. C. Medesan, D. Matesoi, C. Radu, V. Ghetie, and E. S. Ward (1997). Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1. J. Immunol. 158: 2211-2217.

    Google Scholar 

  70. R. P. Junghans and C. L. Anderson (1996). The protection receptor for IgG catabolism is the beta(2)-microglobulin-containing neonatal intestinal transport receptor. Proc. Natl. Acad. Sci. U.S.A. 93: 5512-5516.

    Google Scholar 

  71. D. M. Roberts, M. Guenthert, and R. Rodewald (1990). Isolation and characterization of the Fc receptor from the fetal yolk sac of the rat. J. Cell Biol. 111: 1867-1876.

    Google Scholar 

  72. C. Medesan, C. Radu, J. K. Kim, V. Ghetie, and E. S. Ward (1996). Localization of the site of the IgG molecule that regulates maternofetal transmission in mice. Eur. J. Immunol. 26: 2533-2536.

    Google Scholar 

  73. N. E. Simister, C. M. Story, H. L. Chen, and J. S. Hunt (1996). An IgG-transporting Fc receptor expressed in the syncytiotro-phoblast of human placenta. Eur. J. Immunol. 26: 1527-1531.

    Google Scholar 

  74. E. K. Kristoffersen and R. Matre (1996). Co-localization of the neonatal Fc-gamma receptor and IgG in human placental term syncytiotrophoblasts. Eur. J. Immunol. 26: 1668-1671.

    Google Scholar 

  75. J. L. Leach, D. D. Sedmak, J. M. Osborne, B. Rahill, M. D. Lairmore, and C. L. Anderson (1996). Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast-implications for maternal-fetal antibody transport. J. Immunol. 157: 3317-3322.

    Google Scholar 

  76. J. A. Firth and L. Leach (1996). Not trophoblast alone: a review of the contribution of the fetal microvasculature to transplacental exchange. Placenta 17: 89-96.

    Google Scholar 

  77. D. Velin, H. Acha Orbea, and J. P. Kraehenbuhl (1996). The neonatal Fc receptor is not required for mucosal infection by mouse mammary tumor virus. J. Virol. 70: 7250-7254.

    Google Scholar 

  78. D. L. Watson (1980). Immunological functions of the mammary gland and its secretion—comparative review. Australian J. Biol. Sci. 33: 403-422.

    Google Scholar 

  79. F. W. R. Brambell, W. A. Hemmings, and I. G. Morris (1964). Nature 203: 1352-1355.

    Google Scholar 

  80. F. W. Brambell (1966). The transmission of immunity from mother to young and the catabolism of immunoglobulins. Lancet 2: 1087-1093.

    Google Scholar 

  81. D. R. Abrahamson and R. Rodewald (1981). Evidence for the sorting of endocytic vesicle components during the receptor-mediated transport of IgG across the newborn rat intestine. J. Cell Biol. 91: 270-280.

    Google Scholar 

  82. N. Benlounes, R. Chedid, F. Thuillier, J. F. Desjeux, F. Rousselet, and M. Heyman (1995). Intestinal transport and processing of immunoglobuling in the neonatal and adult rat. Biol. Neonate 67: 254-263.

    Google Scholar 

  83. E. J. Israel, D. F. Wilsker, K. C. Hayes, D. Schoenfeld, and N. E. Simister (1996). Increased clearance of IgG in mice that lack beta(2)-microg lobulin — possible protective role of FcRn. Immunology 89: 573-578.

    Google Scholar 

  84. V. Ghetie, J. G. Hubbard, J.-K. Kim, M.-F. Tsen, L. Yukfung, and E. S. Ward (1996). Abnormally short serum half-lives of IgG in β2-mciroglubul in-deficient mice. Eur. J. Immunol. 26: 690-696.

    Google Scholar 

  85. Legler et al. (1998). J. Exp. Med. 187: 665-660.

    Google Scholar 

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  1. Walter Hunziker
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  2. Jean-Pierre Kraehenbuhl
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Hunziker, W., Kraehenbuhl, JP. Epithelial Transcytosis of Immunoglobulins. J Mammary Gland Biol Neoplasia 3, 287–302 (1998). https://doi.org/10.1023/A:1018715511178

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