The vulnerable mucosae are persistently exposed to airborne, ingested, and sexually transmitted potentially harmful agents. First-line protection of the mucosal surface area, encompassing about 400 m2 in an adult human, depends on active export of secretory IgA (SIgA) and, to some extent, secretory IgM (SIgM) antibodies (Brandtzaeg et al., 1999c) (Fig. 5.1). This secretory immune system is distinct from the systemic counterpart and is operational earlier in ontogeny. Production of SIgA relies on a predominant class switch to the IgA isotypes and a high expression level of the joining (J) chain in mucosal plasma cells (PCs) to ensure adequate production of polymeric IgA (pIgA; mostly dimers) (Brandtzaeg, 1974; Brandtzaeg et al., 1999a). These processes depend on transcriptional activation of the IgA germline (CHα) genes and the J-chain gene. Active epithelial export of pIgA requires abundant expression of the epithelial polymeric Ig receptor (pIgR), because this transport protein is sacrificed with the delivery of its cargo (see Chapter 3). The crucial importance of the J-chain and the pIgR for epithelial transport of pIgA is highlighted by the absence of SIgA in knockout mice deficient for either of these genes (Hendrickson et al., 1995; Johansen et al., 1999; Lycke et al., 1999; Shimada et al., 1999).
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References
Ackermann, L. W., and Denning, G. M. (2004). Nuclear factor-AB contributes to interleukin-4- and interferon-dependent polymeric immunoglobulin receptor expression in human intestinal epithelial cells. Immunology 111:75–85.
Austin, A. S., Haas, K. M., Naugler, S. M., Bajer, A. A., Garcia-Tapia, D., and Estes, D. M. (2003). Identification and characterization of a novel regulatory factor: IgA-inducing protein. J. Immunol. 171:1336–1342.
Bakos, M. A., Kurosky, A., Czerwinski, E. W., and Goldblum, R. M. (1993). A conserved binding site on the receptor for polymeric Ig is homologous to CDR1 of Ig V g domains. J. Immunol. 151: 1346–1352.
Barton, G. M., and Medzhitov, R. (2004). Toll signaling: RIPping off the TNF pathway. Nat. Immunol. 5:472–474.
Ben-Neriah, Y., and Schmitz, M. L. (2004). Of mice and men. EMBO Rep. 5:668–673.
Bentley, A. M., Durham, S. R., Robinson, D. S., Menz, G., Storz, C., Cromwell, O., Kay, A. B., and Wardlaw, A. J. (1993). Expression of endothelial and leukocyte adhesion molecules interacellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in the bronchial mucosa in steady-state and allergen-induced asthma. J. Allergy Clin. Immunol. 92+857–868.
Berstad, A. E., and Brandtzaeg, P. (1998). Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract. Gut 42:522–529.
Bertrand, F. E., 3rd, Billips, L. G., Gartland, G. L., Kubagawa, H., and Schroeder, H. W., Jr. (1996). The J chain gene is transcribed during B and T lymphopoiesis in humans. J. Immunol. 156:4240–4244.
Blanch, V. J., Piskurich, J. F., and Kaetzel, C. S. (1999). Cutting edge: Coordinate regulation of IFN regulatory factor-1 and the polymeric Ig receptor by pro-inflammatory cytokines. J. Immunol. 162:1232–1235.
Braathen, R., Sorensen, V., Brandtzaeg, P., Sandlie, I., and Johansen, F. E. (2002). The carboxyl-terminal domains of IgA and IgM direct isotype-specific polymerization and interaction with the polymeric immunoglobulin receptor. J. Biol. Chem. 277:42, 755–42, 762.
Brandtzaeg, P. (1974). Presence of J chain in human immunocytes containing various immunoglobulin classes. Nature 252:418–420.
Brandtzaeg, P. (1975). Human secretory immunoglobulin M. An immunochemical and immunohistochemical study. Immunology 29:559–570.
Brandtzaeg, P. (1977). Human secretory component—VI. Immunoglobulin-binding properities. Immunochemistry 14:179–188.
Brandtzaeg, P. (1985). Role of J chain and secretory component in receptor-mediated glandular and hepatic transport of immunoglobulins in man. Scand. J. Immunol. 22:111–146.
Brandtzaeg, P., Baekkevold, E. S., Farstad, I. N., Jahnsen, F. L., Johansen, F. E., Nilsen, E. M., and Yamanaka, T. (1999a). Regional specialization in the mucosal immune system: what happens in the microcompartments? Immunol. Today 20:141–151.
Brandtzaeg, P., Carlsen, H. S., and Halstensen, T. S. (2005). The B-cell system in inflammatory bowel disease. In Blumberg, R. S. and Neurath, M. F. (eds.), Immune Mechanisms in Inflammatory Bowel Disease, Springer Publishing, New York, pp. 151–170.
Brandtzaeg, P., Farstad, I. N., and Haraldsen, G. (1999b). Regional specialization in the mucosal immune system: Primed cells do not always home along the same track. Immunol. Today 20:267–277.
Brandtzaeg, P., Farstad, I. N., Johansen, F. E., Morton, H. C., Norderhaug, I. N., and Yamanaka, T. (1999c). The B-cell system of human mucosae and exocrine glands. Immunol. Rev. 171:45–87.
Brandtzaeg, P., Halstensen, T. S., Huitfeldt, H. S., Krajci, P., Kvale, D., Scott, H., and Thrane, P. S. (1992). Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract. Ann. NY Acad. Sci. 664:157–179.
Brandtzaeg, P., and Johansen, F. E. (2001). Confusion about the polymeric Ig receptor. Trends Immunol. 22:545–546.
Brandtzaeg, P., and Johansen, F. E. (2005). Mucosal B cells: Phenotypic characteristics, transcriptional regulation, and homing properties. Immunol. Rev. 206:32–63.
Brandtzaeg, P., Nilssen, D. E., Rognum, T. O., and Thrane, P. S. (1991). Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol. Clin. North Am. 20:397–439.
Brandtzaeg, P., and Prydz, H. (1984). Direct evidence for an integrated function of J chain and secretory component in epithelial transport of immunoglobulins. Nature 311:71–73.
Brandtzaeg, P., and Tolo, K. (1977). Mucosal penetrability enhanced by serum-derived antibodies. Nature 266:262–263.
Bruno, M. E., and Kaetzel, C. S. (2005). Long-term exposure of the HT-29 human intestinal epithelial cell line to TNF causes sustained up-regulation of the polymeric Ig receptor and pro-inflammatory genes through transcriptional and posttranscriptional mechanisms. J. Immunol. 174:7278–7284.
Bruno, M. E., West, R. B., Schneeman, T. A., Bresnick, E. H., and Kaetzel, C. S. (2004). Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene. Mol. Immunol. 40:695–708.
Butcher, E. C., and Picker, L. J. (1996). Lymphocyte homing and homeostasis. Science 272:60–66.
Buts, J. P., and Delacroix, D. L. (1985). Ontogenic changes in secretory component expression by villous and crypt cells of rat small intestine. Immunology 54:181–187.
Campbell, D. J., and Butcher, E. C. (2002). Intestinal attraction: CCL25 functions in effector lymphocyte recruitment to the small intestine. J. Clin. Invest. 110:1079–1081.
Cario, E., and Podolsky, D. K. (2000). Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68:7010–7017.
Castigli, E., Wilson, S. A., Garibyan, L., Rachid, R., Bonilla, F., Schneider, L., and Geha, R. S. (2005a). TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat. Genet. 37:829–834.
Castigli, E., Wilson, S. A., Scott, S., Dedeoglu, F., Xu, S., Lam, K. P., Bram, R. J., Jabara, H., and Geha, R. S. (2005b). TACI and BAFF-R mediate isotype switching in B cells. J. Exp. Med. 201:35–39.
Cerutti, A., Qiao, X., and He, B. (2005). Plasmacytoid dendritic cells and the regulation of immunoglobulin heavy chain class switching. Immunol. Cell. Biol. 83:554–562.
Chintalacharuvu, K. R., Tavill, A. S., Louis, L. N., Vaerman, J. P., Lamm, M. E., and Kaetzel, C. S. (1994). Disulfide bond formation between dimeric immunoglobulin A and the polymeric immunoglobulin receptor during hepatic transcytosis. Hepatology 19:162–173.
Chintalacharuvu, K. R., Vuong, L. U., Loi, L. A., Larrick, J. W., and Morrison, S. L. (2001). Hybrid IgA2/IgG1 antibodies with tailor-made effector functions. Clin. Immunol. 101:21–31.
Chothia, C., and Lesk, A. M. (1987). Canonical structures for the hypervariable regions of immunoglobulins. J. Mol. Biol. 196:901–917.
Conley, M. E., and Delacroix, D. L. (1987). Intravascular and mucosal immunoglobulin A: Two separate but related systems of immune defense? Ann. Intern. Med. 106:892–899.
Coyne, R. S., Siebrecht, M., Peitsch, M. C., and Casanova, J. E. (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. 269:31, 620–31, 625.
Denning, G. M. (1996). IL-4 and IFN-D synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. Role of protein tyrosine kinases. J. Immunol. 156:4807–4814.
Dickinson, B. L., Badizadegan, K., Wu, Z., Ahouse, J. C., Zhu, X., Simister, N. E., Blumberg, R. S., and Lencer, W. I. (1999). Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J. Clin. Invest, 104:903–911.
Erlandsson, L., Andersson, K., Sigvardsson, M., Lycke, N., and Leanderson, T. (1998). Mice with an inactivated joining chain locus have perturbed IgM secretion. Eur. J. Immunol. 28:2355–2365.
Fernandez, M. I., Pedron, T., Tournebize, R., Olivo-Marin, J. C., Sansonetti, P. J., and Phalipon, A. (2003). Anti-inflammatory role for intracellular dimeric immunoglobulin a by neutralization of lipopolysaccharide in epithelial cells. Immunity 18:739–749.
Fujioka, H., Emancipator, S. N., Aikawa, M., Huang, D. S., Blatnik, F., Karban, T., DeFife, K., and Mazanec, M. B. (1998). Immunocytochemical colocalization of specific immunoglobulin A with sendai virus protein in infected polarized epithelium. J. Exp. Med. 188:1223–1229.
Ghetie, V., and Ward, E. S. (2000). Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annu. Rev. Immunol. 18:739–766.
Giffroy, D., Courtoy, P. J., and Vaerman, J. P. (2001). Polymeric IgA binding to the human pIgR elicits intracellular signalling, but fails to stimulate pIgR-transcytosis. Scand. J. Immunol. 53:56–64.
Haelens, A., Verrijdt, G., Schoenmakers, E., Alen, P., Peeters, B., Rombauts, W., and Claessens, F. (1999). The first exon of the human sc gene contains an androgen responsive unit and an interferon regulatory factor element. Mol. Cell. Endocrinol. 153:91–102.
Halpern, M. S., and Koshland, M. E. (1970). Noval subunit in secretory IgA. Nature 228:1276–1278.
Hamburger, A. E., West, A. P., Jr., and Bjorkman, P. J. (2004). Crystal structure of a polymeric immunoglobulin binding fragment of the human polymeric immunoglobulin receptor. Structure 12:1925–1935.
Hamuro, K., Suetake, H., Saha, N. R., Kikuchi, K., and Suzuki, Y., (2007). A Teleost polymeric Ig receptor exhibiting two Ig-like domains transports tetrameric IgM into the skin. J. Immunonl. 178:5682–5689.
Hanson, L. A. (1961). Comparative immunological studies of the immune globulins of human milk and of blood serum. Int. Arch. Allergy Appl. Immunol. 18:241–267.
Hanson, L. A., and Brandtzaeg, P. (1993). The discovery of secretory IgA and the mucosal immune system. Immunol. Today 14:416–417.
Hempen, P. M., Phillips, K. M., Conway, P. S., Sandoval, K. H., Schneeman, T. A., Wu, H. J., and Kaetzel, C. S. (2002). Transcriptional regulation of the human polymeric Ig receptor gene: analysis of basal promoter elements. J. Immunol. 169:1912–1921.
Hendrickson, B. A., Conner, D. A., Ladd, D. J., Kendall, D., Casanova, J. E., Corthésy, B., Max, E. E., Neutra, M. R., Seidman, C. E., and Seidman, J. G. (1995). Altered hepatic transport of immunoglobulin A in mice lacking the J chain. J. Exp. Med. 182:1905–1911.
Hexham, J. M., White, K. D., Carayannopoulos, L. N., Mandecki, W., Brisette, R., Yang, Y. S., and Capra, J. D. (1999). A human immunoglobulin (Ig) A CC3 domain motif directs polymeric Ig receptor-mediated secretion. J. Exp. Med. 189:747–752.
Hieshima, K., Kawasaki, Y., Hanamoto, H., Nakayama, T., Nagakubo, D., Kanamaru, A., and Yoshie, O. (2004). CC chemokine ligands 25 and 28 play essential roles in intestinal extravasation of IgA antibody-secreting cells. J. Immunol. 173:3668–3675.
Hohman, V. S., Stewart, S. E., Rumfelt, L. L., Greenberg, A. S., Avila, D. W., Flajnik, M. F., and Steiner, L. A. (2003). J chain in the nurse shark: implications for function in a lower vertebrate. J. Immunol. 170:6016–6023.
Holmgren, J., and Czerkinsky, C. (2005). Mucosal immunity and vaccines. Nat. Med. 11:S45–S53.
Hooper, L. V., Wong, M. H., Thelin, A., Hansson, L., Falk, P. G., and Gordon, J. I. (2001). Molecular analysis of commensal host-microbial relationships in the intestine. Science 291:881–884.
Iwata, M., Eshima, Y., and Kagechika, H. (2003). Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors. Int. Immunol. 15:1017–1025.
Jahnsen, F. L., Haraldsen, G., Aanesen, J. P., Haye, R., and Brandtzaeg, P. (1995). Eosinophil infiltration is related to increased expression of vascular cell adhesion molecule-1 in nasal polyps. Am. J. Respir. Cell. Mol. Biol. 12:624–632.
Jenkins, S. L., Wang, J., Vazir, M., Vela, J., Sahagun, O., Gabbay, P., Hoang, L., Diaz, R. L., Aranda, R., and Martâin, M. G. (2003). Role of passive and adaptive immunity in influencing enterocyte-specific gene expression. Am. J. Physiol.: Gastrointest. Liver Physiol. 285:G714–G725.
Johansen, F. E., Baekkevold, E. S., Carlsen, H. S., Farstad, I. N., Soler, D., and Brandtzaeg, P. (2005). Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: Dispersion from tonsils. Blood 106:593–600.
Johansen, F. E., Bosloven, B. A., Krajci, P., and Brandtzaeg, P. (1998). A composite DNA element in the promoter of the polymeric immunoglobulin receptor regulates its constitutive expression. Eur. J. Immunol. 28:1161–1171.
Johansen, F. E., Braathen, R., and Brandtzaeg, P. (2000). Role of J chain in secretory immunoglobulin formation. Scand. J. Immunol. 52:240–248.
Johansen, F. E., Braathen, R., and Brandtzaeg, P. (2001). The J chain is essential for polymeric Ig receptor-mediated epithelial transport of IgA. J. Immunol. 167:5185–5192.
Johansen, F. E., and Brandtzaeg, P. (2004). Transcriptional regulation of the mucosal IgA system. Trends Immunol. 25:150–157.
Johansen, F. E., Pekna, M., Norderhaug, I. N., Haneberg, B., Hietala, M. A., Krajci, P., Betsholtz, C., and Brandtzaeg, P. (1999). Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice. J. Exp. Med. 190:915–922.
Johansson-Lindbom, B., Svensson, M., Wurbel, M. A., Malissen, B., Marquez, G., and Agace, W. (2003). Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): Requirement for GALT dendritic cells and adjuvant. J. Exp. Med. 198:963–969.
Kaetzel, C. S. (2005). The polymeric immunoglobulin receptor: Bridging innate and adaptive immune responses at mucosal surfaces. Immunol. Rev. 206:83–99.
Kaetzel, C. S., Blanch, V. J., Hempen, P. M., Phillips, K. M., Piskurich, J. F., and Youngman, K. R. (1997). The polymeric immunoglobulin receptor: structure and synthesis. Biochem. Soc. Trans. 25:475–480.
Kaetzel, C. S., Robinson, J. K., Chintalacharuvu, K. R., Vaerman, J. P., and Lamm, M. E. (1991). The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: A local defense function for IgA. Proc. Natl. Acad. Sci. USA 88:8796–8800.
Kang, C. J., Sheridan, C., and Koshland, M. E. (1998). A stage-specific enhancer of immunoglobulin J chain gene is induced by interleukin-2 in a presecretor B cell stage. Immunity 8:285–295.
Khattar, N. H., Lele, S. M., and Kaetzel, C. S. (2005). Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: Correlation with dysregulated expression of the transcription factors USF and AP2. J. Biomed. Sci. 12:65–77.
Kiyono, H., and Fukuyama, S. (2004). NALT- versus Peyer’s-patch-mediated mucosal immunity. Nat. Rev. Immunol. 4:699–710.
Kopp, E., and Medzhitov, R. (2003). Recognition of microbial infection by Toll-like receptors. Curr. Opin. Immunol. 15:396–401.
Kraehenbuhl, J. P., and Neutra, M. R. (2000). Epithelial M cells: Differentiation and function. Annu. Rev. Cell. Dev. Biol. 16:301–332.
Krugmann, S., Pleass, R. J., Atkin, J. D., and Woof, J. M. (1997). Structural requirements for assembly of dimeric IgA probed by site-directed mutagenesis of J chain and a cysteine residue of the q-chain CH2 domain. J. Immunol. 159:244–249.
Kunkel, E. J., Campbell, D. J., and Butcher, E. C. (2003). Chemokines in lymphocyte trafficking and intestinal immunity. Microcirculation 10:313–323.
Kunkel, E. J., Campbell, J. J., Haraldsen, G., Pan, J., Boisvert, J., Roberts, A. I., Ebert, E. C., Vierra, M. A., Goodman, S. B., Genovese, M. C., et al. (2000). Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J. Exp. Med. 192:761–768.
Kvale, D., and Brandtzaeg, P. (1995). Constitutive and cytokine induced expression of HLA molecules, secretory component, and intercellular adhesion molecule-1 is modulated by butyrate in the colonic epithelial cell line HT-29. Gut 36:737–742.
Lansford, R. D., McFadden, H. J., Siu, S. T., Cox, J. S., Cann, G. M., and Koshland, M. E. (1992). A promoter element that exerts positive and negative control of the interleukin 2-responsive J-chain gene. Proc. Natl. Acad. Sci. USA 89:5966–5970.
Lawrence, T., Bebien, M., Liu, G. Y., Nizet, V., and Karin, M. (2005). IKKL limits macrophage NF- B activation and contributes to the resolution of inflammation. Nature 434:1138–1143.
Li, T. W., Wang, J., Lam, J. T., Gutierrez, E. M., Solorzano-Vargus, R. S., Tsai, H. V., and Martin, M. G. (1999). Transcriptional control of the murine polymeric IgA receptor promoter by glucocorticoids. Am. J. Physiol. 276:G1425–G1434.
Lin, K. I., Angelin-Duclos, C., Kuo, T. C., and Calame, K. (2002). Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells to immunoglobulin M-secreting plasma cells. Mol. Cell. Biol. 22:4771–4780.
Lin, Y. C., and Stavnezer, J. (1992). Regulation of transcription of the germ-line Ig constant region gene by an ATF element and by novel transforming growth factor-f1-responsive elements. J. Immunol. 149:2914–2925.
Linderson, Y., Eberhard, D., Malin, S., Johansson, A., Busslinger, M., and Pettersson, S. (2004). Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5-mediated repression of B-cell-specific genes. EMBO Rep. 5:291–296.
Litinskiy, M. B., Nardelli, B., Hilbert, D. M., He, B., Schaffer, A., Casali, P., and Cerutti, A. (2002). DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3:822–829.
Lycke, N., Erlandsson, L., Ekman, L., Schèon, K., and Leanderson, T. (1999). Lack of J chain inhibits the transport of gut IgA and abrogates the development of intestinal antitoxic protection. J. Immunol. 163:913–919.
Macdonald, T. T., and Monteleone, G. (2005). Immunity, inflammation, and allergy in the gut. Science 307:1920–1925.
Mackie, R. I., Sghir, A., and Gaskins, H. R. (1999). Developmental microbial ecology of the neonatal gastrointestinal tract. Am. J. Clin. Nutr. 69:1035S–1045S.
Manis, J. P., Tian, M., and Alt, F. W. (2002). Mechanism and control of class-switch recombination. Trends Immunol. 23:31–39.
Manz, R. A., Hauser, A. E., Hiepe, F., and Radbruch, A. (2005). Maintenance of serum antibody levels. Annu. Rev. Immunol. 23:367–386.
Martin, M. G., Wang, J., Li, T. W., Lam, J. T., Gutierrez, E. M., Solorzano-Vargas, R. S., and Tsai, A. H. (1998). Characterization of the 5'-flanking region of the murine polymeric IgA receptor gene. Am. J. Physiol. 275:G778–G788.
Mazanec, M. B., Coudret, C. L., and Fletcher, D. R. (1995). Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies. J. Virol. 69:1339–1343.
Mazanec, M. B., Kaetzel, C. S., Lamm, M. E., Fletcher, D., and Nedrud, J. G. (1992). Intracellular neutralization of virus by immunoglobulin A antibodies. Proc. Natl. Acad. Sci. USA 89:6901–6905.
Mazanec, M. B., Nedrud, J. G., Kaetzel, C. S., and Lamm, M. E. (1993). A three-tiered view of the role of IgA in mucosal defense. Immunol. Today 14:430–435.
Mestecky, J., and Russell, M. W. (1986). IgA subclasses. Monogr. Allergy 19:277–301.
Mestecky, J., Zikan, J., and Butler, W. T. (1971). Immunoglobulin M and secretory immunoglobulin A: Presence of a common polypeptide chain different from light chains. Science 171:1163–1165.
Mora, J. R., Bono, M. R., Manjunath, N., Weninger, W., Cavanagh, L. L., Rosemblatt, M., and Von Andrian, U. H. (2003). Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 424:88–93.
Mosmann, T. R., Gravel, Y., Williamson, A. R., and Baumal, R. (1978). Modification and fate of J chain in myeloma cells in the presence and absence of polymeric immunoglobulin secretion. Eur. J. Immunol. 8:94–101.
Mostov, K., and Kaetzel, C. S. (1999). Immunoglobulin transport and the polymeric immunoglobulin receptor. In Ogra, P. L., Mestecky, J., Lamm, M. E. , Strober, W., Bienenstock, J., and McGhee, J. R. (eds.), Mucosal Immunology. Academic Press, San Diego, pp. 181–211.
Nakamura, Y., Nosaka, S., Suzuki, M., Nagafuchi, S., Takahashi, T., Yajima, T., Takenouchi-Ohkubo, N., Iwase, T., and Moro, I. (2004). Dietary fructooligosaccharides up-regulate immunoglobulin A response and polymeric immunoglobulin receptor expression in intestines of infant mice. Clin. Exp. Immunol. 137:52–58.
Natvig, I. B., Johansen, F. E., Nordeng, T. W., Haraldsen, G., and Brandtzaeg, P. (1997). Mechanism for enhanced external transfer of dimeric IgA over pentameric IgM: Studies of diffusion, binding to the human polymeric Ig receptor, and epithelial transcytosis. J. Immunol. 159:4330–4340.
Nilsen, E. M., Johansen, F. E., Kvale, D., Krajci, P., and Brandtzaeg, P. (1999). Different regulatory pathways employed in cytokine-enhanced expression of secretory component and epithelial HLA class I genes. Eur. J. Immunol. 29:168–179.
Norderhaug, I. N., Johansen, F. E., Krajci, P., and Brandtzaeg, P. (1999a). Domain deletions in the human polymeric Ig receptor disclose differences between its dimeric IgA and pentameric IgM interaction. Eur. J. Immunol. 29:3401–3409.
Norderhaug, I. N., Johansen, F. E., Schjerven, H., and Brandtzaeg, P. (1999b). Regulation of the formation and external transport of secretory immunoglobulins. Crit. Rev. Immunol. 19:481–508.
Odendahl, M., Mei, H., Hoyer, B. F., Jacobi, A. M., Hansen, A., Muehlinghaus, G., Berek, C., Hiepe, F., Manz, R., Radbruch, A., and Dorner, T. (2005). Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood 105:1614–1621.
Pabst, O., Ohl, L., Wendland, M., Wurbel, M. A., Kremmer, E., Malissen, B., and Forster, R. (2004). Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine. J. Exp. Med. 199:411–416.
Pal, K., Kaetzel, C. S., Brundage, K., Cunningham, C. A., and Cuff, C. F. (2005). Regulation of polymeric immunoglobulin receptor expression by reovirus. J. Gen. Virol. 86:2347–2357.
Persson, C. G., Erjefalt, J. S., Greiff, L., Andersson, M., Erjefalt, I., Godfrey, R. W., Korsgren, M., Linden, M., Sundler, F., and Svensson, C. (1998). Plasma-derived proteins in airway defence, disease and repair of epithelial injury. Eur. Respir. J. 11:958–970.
Phalipon, A., and Corthésy, B. (2003). Novel functions of the polymeric Ig receptor: Well beyond transport of immunoglobulins. Trends Immunol. 24:55–58.
Piskurich, J. F., Youngman, K. R., Phillips, K. M., Hempen, P. M., Blanchard, M. H., France, J. A., and Kaetzel, C. S. (1997). Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-n. Mol. Immunol. 34:75–91.
Qiu, G., and Stavnezer, J. (1998). Overexpression of BSAP/Pax-5 inhibits switching to IgA and enhances switching to IgE in the I.29 mu B cell line. J. Immunol. 161:2906–2918.
Quiding-Jarbrink, M., Nordstrom, I., Granstrom, G., Kilander, A., Jertborn, M., Butcher, E. C., Lazarovits, A. I., Holmgren, J., and Czerkinsky, C. (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.
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., and Medzhitov, R. (2004). Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118:229–241.
Randall, T. D., Heath, A. W., Santos-Argumedo, L., Howard, M. C., Weissman, I. L., and Lund, F. E. (1998). Arrest of B lymphocyte terminal differentiation by CD40 signaling: Mechanism for lack of antibody-secreting cells in germinal centers. Immunity 8:733–742.
Rao, S., Karray, S., Gackstetter, E. R., and Koshland, M. E. (1998). Myocyte enhancer factor-related B-MEF2 is developmentally expressed in B cells and regulates the immunoglobulin J chain promoter. J. Biol. Chem. 273:26, 123–129.
Rinkenberger, J. L., Wallin, J. J., Johnson, K. W., and Koshland, M. E. (1996). An interleukin-2 signal relieves BSAP (Pax5)-mediated repression of the immunoglobulin J chain gene. Immunity 5:377–386.
Robinson, J. K., Blanchard, T. G., Levine, A. D., Emancipator, S. N., and Lamm, M. E. (2001). A mucosal IgA-mediated excretory immune system in vivo. J. Immunol. 166:3688–3692.
Roe, M., Norderhaug, I. N., Brandtzaeg, P., and Johansen, F. E. (1999). Fine specificity of ligand-binding domain 1 in the polymeric Ig receptor: Importance of the CDR2-containing region for IgM interaction. J. Immunol. 162:6046–6052.
Salmi, M., and Jalkanen, S. (2005). Lymphocyte homing to the gut: Attraction, adhesion, and commitment. Immunol. Rev. 206:100–113.
Schjerven, H., Brandtzaeg, P., and Johansen, F. E. (2000). Mechanism of IL-4-mediated up-regulation of the polymeric Ig receptor: Role of STAT6 in cell type-specific delayed transcriptional response. J. Immunol. 165:3898–3906.
Schjerven, H., Brandtzaeg, P., and Johansen, F. E. (2001). A novel NF-S B/Rel site in intron 1 cooperates with proximal promoter elements to mediate TNF-d-induced transcription of the human polymeric Ig receptor. J. Immunol. 167:6412–6420.
Schjerven, H., Brandtzaeg, P., and Johansen, F. E. (2003). Hepatocyte NF-1 and STAT6 cooperate with additional DNA-binding factors to activate transcription of the human polymeric Ig receptor gene in response to IL-4. J. Immunol. 170:6048–6056.
Schjerven, H., Tran, T. N., Brandtzaeg, P., and Johansen, F. E. (2004). De novo synthesized RelB mediates TNF-induced up-regulation of the human polymeric Ig receptor. J. Immunol. 173:1849–1857.
Schmeck, B., Zahlten, J., Moog, K., van Laak, V., Huber, S., Hocke, A. C., Opitz, B., Hoffmann, E., Kracht, M., Zerrahn, J., et al. (2004). Streptococcus pneumoniae-induced p38 MAPK-dependent phosphorylation of RelA at the interleukin-8 promotor. J. Biol. Chem. 279:53, 241–53, 247.
Schneeman, T. A., Bruno, M. E., Schjerven, H., Johansen, F. E., Chady, L., and Kaetzel, C. S. (2005). Regulation of the polymeric Ig receptor by signaling through TLRs 3 and 4: Linking innate and adaptive immune responses. J. Immunol. 175:376–384.
Senftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krahn, G., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S. C., and Karin, M. (2001). Activation by IKKa of a second, evolutionary conserved, NF-oB signaling pathway. Science 293:1495–1499.
Shi, M. J., Park, S. R., Kim, P. H., and Stavnezer, J. (2001). Roles of Ets proteins, NF-eB and nocodazole in regulating induction of transcription of mouse germline Ig B RNA by transforming growth factor- 1. Int. Immunol. 13:733–746.
Shi, M. J., and Stavnezer, J. (1998). CBF S3 (AML2) is induced by TGF-31 to bind and activate the mouse germline Ig s promoter. J. Immunol. 161:6751–6760.
Shimada, S., Kawaguchi-Miyashita, M., Kushiro, A., Sato, T., Nanno, M., Sako, T., Matsuoka, Y., Sudo, K., Tagawa, Y., Iwakura, Y., and Ohwaki, M. (1999). Generation of polymeric immunoglobulin receptor-deficient mouse with marked reduction of secretory IgA. J. Immunol. 163:5367–5373.
Shin, M. K., and Koshland, M. E. (1993). Ets-related protein PU.1 regulates expression of the immunoglobulin J-chain gene through a novel Ets-binding element. Genes Dev. 7:2006–2015.
Tarkowski, A., Lue, C., Moldoveanu, Z., Kiyono, H., McGhee, J. R., and Mestecky, J. (1990). Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses. J. Immunol. 144:3770–3778.
Tigges, M. A., Casey, L. S., and Koshland, M. E. (1989). Mechanism of interleukin-2 signaling: Mediation of different outcomes by a single receptor and transduction pathway. Science 243:781–786.
Tomasi, T. B. (1992). The discovery of secretory IgA and the mucosal immune system. Immunol. Today 13:416–418.
Tomasi, T. B., Jr., Tan, E. M., Solomon, A., and Prendergast, R. A. (1965). Characteristics of an immune system common to certain external secretions. J. Exp. Med. 121:101–124.
Vermeulen, L., De Wilde, G., Notebaert, S., Vanden Berghe, W., and Haegeman, G. (2002). Regulation of the transcriptional activity of the nuclear factor-cB p65 subunit. Biochem. Pharmacol. 64:963–970.
Wallin, J. J., Gackstetter, E. R., and Koshland, M. E. (1998). Dependence of BSAP repressor and activator functions on BSAP concentration. Science 279:1961–1964.
Wallin, J. J., Rinkenberger, J. L., Rao, S., Gackstetter, E. R., Koshland, M. E., and Zwollo, P. (1999). B cell-specific activator protein prevents two activator factors from binding to the immunoglobulin J chain promoter until the antigen-driven stages of B cell development. J. Biol. Chem. 274:15, 959–15, 965.
White, K. D., and Capra, J. D. (2002). Targeting mucosal sites by polymeric immunoglobulin receptor-directed peptides. J. Exp. Med. 196:551–555.
Woof, J. M., and Mestecky, J. (2005). Mucosal immunoglobulins. Immunol. Rev. 206:64–82.
Xu, X., Sun, Y. L., and Hoey, T. (1996). Cooperative DNA binding and sequence-selective recognition conferred by the STAT amino-terminal domain. Science 273:794–797.
Yoshida, M., Claypool, S. M., Wagner, J. S., Mizoguchi, E., Mizoguchi, A., Roopenian, D. C., Lencer, W. I., and Blumberg, R. S. (2004). Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity 20:769–783.
Youngman, K. R., Fiocchi, C., and Kaetzel, C. S. (1994). Inhibition of IFN-Y activity in supernatants from stimulated human intestinal mononuclear cells prevents up-regulation of the polymeric Ig receptor in an intestinal epithelial cell line. J. Immunol. 153:675–681.
Zhang, Y., and Derynck, R. (2000). Transcriptional regulation of the transforming growth factor-Z-inducible mouse germ line Ig - constant region gene by functional cooperation of Smad, CREB, and AML family members. J. Biol. Chem. 275:16, 979–985.
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Johansen, FE., Braathen, R., Munthe, E., Schjerven, H., Brandtzaeg, P. (2007). Regulation of the Mucosal IgA System. In: Kaetzel, C.S. (eds) Mucosal Immune Defense: Immunoglobulin A. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72232-0_5
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