The intestinal B-cell response in celiac disease

Frontiers in Immunology

Volumn 3, Issue OCT, 2012, Pages

  Mesin, Luka ^a   Sollid, Ludvig M ^a   Di Niro, Roberto ^a,b  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autoantibodies; B cells; Celiac disease; Intestinal mucosa; Mucosal immunity

Indexed keywords

EID: 84874217562     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00313     Document Type: Review

References (156)

1. Abadie, V., Sollid, L. M., Barreiro, L. B., and Jabri, B. (2011). Integration of genetic and immunological insights into a model of celiac disease patho-genesis. Annu. Rev. Immunol. 29, 493-525.
2. Alaedini, A., and Green, P. H. (2008). Autoantibodies in celiac disease. Autoimmunity 41, 19-26.
3. Baklien, K., and Brandtzaeg, P. (1976). Immunohistochemical characterization of local immunoglobulin formation in Crohn's disease of the ileum. Scand. J. Gastroenterol. 11, 447-457.
4. Baklien, K., Brandtzaeg, P., and Fausa, O. (1977). Immunoglobulins in jeju-nal mucosa and serum from patients with adult coeliac disease. Scand. J. Gastroenterol. 12, 149-159.
5. Barone, F., Patel, P., Sanderson, J. D., and Spencer, J. (2009). Gut-associated lymphoid tissue contains the molecular machinery to support T-cell-dependent and T-cell-independent class switch recombination. Mucosal Immunol. 2, 495-503.
6. Barone, F., Vossenkamper, A., Bour-sier, L., Su, W., Watson, A., John, S., et al. (2011). IgA-producing plasma cells originate from germinal centers that are induced by B-cell receptor engagement in humans. Gastroen-terology 140, 947-956.
7. Barr, T. A., Gray, M., and Gray, D. (2012). B cells: programmers of CD4 T cell responses. Infect. Disord. Drug Ta r g e t s 12, 222-231.
8. Bemark, M., Boysen, P., and Lycke, N. Y. (2012). Induction of gut IgA production through T cell-dependent and T cell-independent pathways. Ann. N. Y. Acad. Sci. 1247, 97-116.
9. Benckert, J., Schmolka, N., Kreschel, C., Zoller, M. J., Sturm, A., Wieden-mann, B., etal. (2011). The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J. Clin. Invest. 121, 1946-1955.
10. Benson, M. J., Dillon, S. R., Castigli, E., Geha, R. S., Xu, S., Lam, K. P., et al. (2008). Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J. Immunol. 180, 3655-3659.
11. Bergqvist, P., Gardby, E., Stensson, A., Bemark, M., and Lycke, N. Y. (2006). Gut IgA class switch recombination in the absence of CD40 does not occur in the lamina propria and is independent of germinal centers. J. Immunol. 177, 7772-7783.
12. Bergqvist, P., Stensson, A., Lycke, N. Y., and Bemark, M. (2010). T cell-independent IgA class switch recombination is restricted to the GALT and occurs prior to manifest germinal center formation. J. Immunol. 184, 3545-3553.
13. Bethune, M. T., Borda, J. T., Ribka, E., Liu, M. X., Phillippi-Falkenstein, K., Jandacek, R. J., et al. (2008). A non-human primate model for gluten sensitivity. PLoS ONE 3, e1614. doi: 10.1371/journal.pone.0001614
14. Bjorck, S., Brundin, C., Lorinc, E., Lynch, K. F., and Agardh, D. (2010). Screening detects a high proportion of celiac disease in young HLA-genotyped children. J. Pediatr. Gas-troenterol. Nutr. 50, 49-53.
15. Bolduc, A., Long, E., Stapler, D., Cas-calho, M., Tsubata, T., Koni, P. A., et al. (2010). Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas. J. Immunol. 185, 220-230.
16. Borrelli, M., Maglio, M., Agnese, M., Paparo, F., Gentile, S., Colicchio, B., et al. (2010). High density of intraepithelial gammadelta lymphocytes and deposits of immunoglob-ulin (Ig)M anti-tissue transglutam-inase antibodies in the jejunum of coeliac patients with IgA deficiency. Clin. Exp. Immunol. 160, 199-206.
17. Boursier, L., Dunn-Walters, D. K., and Spencer, J. (1999). Characteristics of IgVH genes used by human intestinal plasma cells from childhood. Immunology 97, 558-564.
18. Boursier, L., Gordon, J. N., Thiag-amoorthy, S., Edgeworth, J. D., and Spencer, J. (2005). Human intestinal IgA response is generated in the organized gut-associated lymphoid tissue but not in the lamina propria. Gastroenterology 128, 1879-1889.
19. Brandtzaeg, P. (2006). The changing immunological paradigm in coeliac disease. Immunol. Lett. 105, 127-139.
20. Brandtzaeg, P., Farstad, I. N., Johansen, F. E., Morton, H. C., Norderhaug, I. N., and Yamanaka, T. (1999). The B-cell system of human mucosae and exocrine glands. Immunol. Rev. 171, 45-87.
21. Brandtzaeg, P., and Johansen, F. E. (2005). Mucosal B cells: pheno-typic characteristics, transcriptional regulation, and homing properties. Immunol. Rev. 206, 32-63.
22. Brandtzaeg, P., and Pabst, R. (2004). Let's go mucosal: communication on slippery ground. Trends Immunol. 25, 570-577.
23. 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.
24. Casola, S., Otipoby, K. L., Alimzhanov, M., Humme, S., Uyttersprot, N., Kutok, J. L., etal. (2004). B cell receptor signal strength determines B cell fate. Nat. Immunol. 5, 317-327.
25. Cerutti,A. (2008). The regulation of IgA class switching. Nat. Rev. Immunol. 8, 421-434.
26. Cerutti, A., Chen, K., and Chorny, A. (2011). Immunoglobulin responses at the mucosal interface. Annu. Rev. Immunol. 29, 273-293.
27. Cerutti, A., and Rescigno, M. (2008). The biology of intestinal immunoglobulin A responses. Immunity 28, 740-750.
28. Chan, T. D., Gatto, D., Wood, K., Camidge, T., Basten, A., and Brink, R. (2009). Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J. Immunol. 183, 3139- 3149.
29. Chorzelski, T. P., Sulej, J., Tchorzewska, H., Jablonska, S., Beutner, E. H., and Kumar, V. (1983). IgA class endomy-sium antibodies in dermatitis her-petiformis and coeliac disease. Ann. N. Y. Acad. Sci. 420, 325-334.
30. Ciclitira, P. J., Ellis, H. J., Wood, G. M., Howdle, P. D., and Losowsky, M. S. (1986). Secretion of gliadin antibody by coeliac jejunal mucosal biopsies cultured in vitro. Clin. Exp. Immunol. 64, 119-124.
31. Crabbe, P. A., Nash, D. R., Bazin, H., Eyssen, D. V., and Heremans, J. F. (1969). Antibodies of the IgA type in intestinal plasma cells of germfree mice after oral or parenteral immunization with ferritin. J. Exp. Med. 130, 723-744.
32. Crawford, A., MacLeod, M., Schumacher, T., Corlett, L., and Gray, D. (2006). Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J. Immunol. 176, 3498-3506.
33. Crouch, E. E., Li, Z., Takizawa, M., Fichtner-Feigl, S., Gourzi, P., Mon-tano, C., et al. (2007). Regulation of AID expression in the immune response. J. Exp. Med. 204, 1145- 1156.
34. Cunningham, A. F., Gaspal, F., Serre, K., Mohr, E., Henderson, I. R., Scott-Tucker, A., et al. (2007). Salmonella induces a switched antibody response without germinal centers that impedes the extracellular spread of infection. J. Immunol. 178, 6200-6207.
35. DePaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., et al. (2011). Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 471, 220-224.
36. Descatoire, M., Weill, J. C., Reynaud, C. A., and Weller, S. (2011). A human equivalent of mouse B-1 cells? J. Exp. Med. 208, 2563-2564; author reply 2566-2569.
37. Di Niro, R., Mesin, L., Raki, M., Zheng, N. Y., Lund-Johansen, F., Lundin, K. E. A., et al. (2010). Rapid generation of rotavirus-specific human monoclonal antibodies from small intestinal mucosa. J. Immunol. 185, 5377-5383.
38. Di Niro, R., Mesin, L., Zheng, N. Y., Stamnaes, J., Morrissey, M., Lee, J. H., et al. (2012). High abundance of plasma cells secreting transglutam-inase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions. Nat. Med. 18, 441-445.
39. Di Niro, R., Sblattero, D., Florian, F., Stebel, M., Zentilin, L., Giacca, M., et al. (2008). Anti-idiotypic response in mice expressing human autoan-tibodies. Mol. Immunol. 45, 1782- 1791.
40. Dieterich, W., Ehnis, T., Bauer, M., Donner, P., Volta, U., Riecken, E. O., et al. (1997). Identification of tissue transglutaminase as the autoanti-gen of celiac disease. Nat. Med. 3, 797-801.
41. Dieterich, W., Laag, E., Schopper, H., Volta, U., Ferguson, A., Gillett, H., et al. (1998). Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 115, 1317-1321.
42. Dieterich, W., Trapp, D., Esslinger, B., Leidenberger, M., Piper, J., Hahn, E., et al. (2003). Autoantibodies of patients with coeliac disease are insufficient to block tissue transglu-taminase activity. Gut 52, 1562-1566.
43. Douglas, A. P., Crabbe, P. A., and Hobbs, J. R. (1970). Immunochem-ical studies on the serum, intestinal secretions and intestinal mucosa in patients with adult celiac disease and other forms of the celiac syndrome. Gastroenterology 59, 414-425.
44. Dunn-Walters, D. K., Boursier, L., and Spencer, J. (1997). Hypermu-tation, diversity and dissemination of human intestinal lamina propria plasma cells. Eur. J. Immunol. 27, 2959-2964.
45. Elgueta, R., Benson, M. J., De Vries, V. C., Wasiuk, A., Guo, Y., and Noelle, R. J. (2009). Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 229, 152-172.
46. Esposito, C., Paparo, F., Caputo, I., Rossi, M., Maglio, M., Sblat-tero, D., et al. (2002). Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutami-nase activity both in vitro and in situ. Gut 51, 177-181.
47. Fagarasan, S., and Honjo, T. (2000). T-Independent immune response: new aspects of B cell biology. Science 290, 89-92.
48. Fagarasan, S., Kawamoto, S., Kanagawa, O., and Suzuki, K. (2010). Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. Annu. Rev. Immunol. 28, 243-273.
49. Fagarasan, S., Kinoshita, K., Mura-matsu, M., Ikuta, K., and Honjo, T. (2001). In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413, 639-643.
50. Farstad, I. N., Carlsen, H., Morton, H. C., and Brandtzaeg, P. (2000). Immunoglobulin A cell distribution in the human small intestine: phenotypic and functional characteristics. Immunology 101, 354-363.
51. Fayette, J., Dubois, B., Vandenabeele, S., Bridon, J. M., Vanbervliet, B., Durand, I., et al. (1997). Human dendritic cells skew isotype switching of CD40-activated naive B cells towards IgA1 and IgA2. J. Exp. Med. 185, 1909-1918.
52. Ferrari, S., Giliani, S., Insalaco, A., Al-Ghonaium, A., Soresina, A. R., Loubser, M., et al. (2001). Mutations of CD40 gene cause an autosomal recessive form of immunodeficiency with hyper IgM. Proc. Natl. Acad. Sci. U.S.A. 98, 12614-12619.
53. Fleckenstein, B., Qiao, S. W., Larsen, M. R., Jung, G., Roepstorff, P., and Sollid, L. M. (2004). Molecular characterization of covalent complexes between tissue transglutaminase and gliadin peptides. J. Biol. Chem. 279, 17607-17616.
54. Foote, J. B., and Kearney, J. F. (2009). Generation of B cell memory to the bacterial polysaccharide alpha-1,3 dextran. J. Immunol. 183, 6359- 6368.
55. Freitag, T. L., Rietdijk, S., Junker, Y., Popov, Y., Bhan, A. K., Kelly, C. P., et al. (2009). Gliadin-primed CD4+CD45RBlowCD25- T cells drive gluten-dependent small intestinal damage after adoptive transfer into lymphopenic mice. Gut 58, 1597-1605.
56. Fujihashi, K., McGhee, J. R., Lue, C., Beagley, K. W., Taga, T., Hirano, T., et al. (1991). Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis. J. Clin. Invest. 88, 248-252.
57. Gibbons, D. L., and Spencer, J. (2011). Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol. 4, 148-157.
58. Gonnella, P. A., Chen, Y., Inobe, J., Komagata, Y., Quartulli, M., and Weiner, H. L. (1998). In situ immune response in gut-associated lymphoid tissue (GALT) following oral antigen in TCR-transgenic mice. J. Immunol. 160, 4708-4718.
59. Green, P. H. (2005). The many faces of celiac disease: clinical presentation of celiac disease in the adult population. Gastroenterology 128, S74-S78.
60. Griffin, D. O., and Rothstein, T. L. (2012). Human B1 cell frequency: isolation and analysis of human B1 cells. Front. Immunol. 3:122. doi: 10.3389/fimmu.2012.00122
61. Guy-Grand, D., Griscelli, C., and Vas-salli, P. (1975). Peyer's patches, gut IgA plasma cells and thymic function: study in nude mice bearing thymic grafts. J. Immunol. 115, 361-364.
62. Halstensen, T. S., Hvatum, M., Scott, H., Fausa, O., and Brandtzaeg, P. (1992). Association of subepithelial deposition of activated complement and immunoglobulin G and M response to gluten in celiac disease. Gastroen-terology 102, 751-759.
63. Halttunen, T., and Maki, M. (1999). Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 116, 566-572.
64. Hansson, T., Dannaeus, A., Kraaz, W., Sjoberg, O., and Klareskog, L. (1997). Production of antibodies to gliadin by peripheral blood lymphocytes in children with celiac disease: the use of an enzyme-linked immunospot technique for screening and follow-up. Pediatr. Res. 41, 554-559.
65. Hapfelmeier, S., Lawson, M. A., Slack, E., Kirundi, J. K., Stoel, M., Heiken-walder, M., et al. (2010). Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328, 1705-1709.
66. Harwood, N. E., and Batista, F. D. (2010). Early events in B cell activation. Annu. Rev. Immunol. 28, 185-210.
67. He, B., Xu, W., Santini, P. A., Poly-dorides, A. D., Chiu, A., Estrella, J., et al. (2007). Intestinal bacteria trigger T cell-independent immuno-globulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26, 812-826.
68. Heiser, R. A., Snyder, C. M., St Clair, J., and Wysocki, L. J. (2011). Aborted germinal center reactions and B cell memory by follicular T cells specific for a B cell receptor V region peptide. J. Immunol. 187, 212-221.
69. Holmes, G. K., Asquith, P., Stokes, P. L., and Cooke, W. T. (1973). Cellular infiltrate of jejunal biopsies in adult coeliac disease (ACD) in relation to gluten withdrawal. Gut 14, 429.
70. Holtmeier, W., Hennemann, A., and Caspary, W. F. (2000). IgA and IgM V(H) repertoires in human colon: evidence for clonally expanded B cells that are widely disseminated. Gas-troenterology 119, 1253-1266.
71. Hooper, L. V., and Macpherson, A. J. (2010). Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159-169.
72. Husby, S., Koletzko, S., Korponay-Szabo, I. R., Mearin, M. L., Phillips, A., Shamir, R., et al. (2012). European Society for Pediatric Gastroen-terology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J. Pediatr. Gastroen-terol. Nutr. 54, 136-160.
73. Jabri, B., and Sollid, L. M. (2009). Tissue-mediated control of immu-nopathology in coeliac disease. Nat. Rev. Immunol. 9, 858-870.
74. Jiang, H. Q., Thurnheer, M. C., Zuercher, A. W., Boiko, N. V., Bos, N. A., and Cebra, J. J. (2004). Interactions of commensal gut microbes with subsets of B- and T-cells in the murine host. Vaccine 22, 805-811.
75. 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.
76. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., and Gordon, J. I. (2011). Human nutrition, the gut microbiome and the immune system. Nature 474, 327-336.
77. Kaukinen, K., Peraaho, M., Collin, P., Partanen, J., Woolley, N., Kaarti-nen, T., et al. (2005). Small-bowel mucosal transglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: a prospective and randomized clinical study. Scand. J. Gastroenterol. 40, 564-572.
78. Kawamoto, S., Tran, T. H., Maruya, M., Suzuki, K., Doi, Y., Tsutsui, Y., et al. (2012). The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science 336, 485-489.
79. Kett, K., Scott, H., Fausa, O., and Brandtzaeg, P. (1990). Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain. Gastroen-terology 99, 386-392.
80. Kilander, A. F., Nilsson, L. A., and Gill-berg, R. (1987). Serum antibodies to gliadin in coeliac disease after gluten withdrawal. Scand. J. Gastroenterol. 22, 29-34.
81. Koninckx, C. R., Giliams, J. P., Polanco, I., and Pena, A. S. (1984). IgA antigliadin antibodies in celiac and inflammatory bowel disease. J. Pedi-atr. Gastroenterol. Nutr. 3, 676-682.
82. Korponay-Szabo, I. R., Halttunen, T., Szalai, Z., Laurila, K., Kiraly, R., Kovacs, J. B., et al. (2004). In vivo targeting of intestinal and extrain-testinal transglutaminase 2 by coeliac autoantibodies. Gut 53, 641-648.
83. Kroese, F. G., Ammerlaan, W. A., Dee-nen, G. J., Adams, S., Herzenberg, L. A., and Kantor, A. B. (1995). A dual origin for IgA plasma cells in the murine small intestine. Adv. Exp. Med. Biol. 371A, 435-440.
84. Labrooy, J. T., Hohmann, A. W., Davidson, G. P., Hetzel, P. A., Johnson, R. B., and Shearman, D. J. (1986). Intestinal and serum antibody in coeliac disease: a comparison using ELISA. Clin. Exp. Immunol. 66, 661-668.
85. Lancaster-Smith, M., Kumar, P., Marks, R., Clark, M. L., and Dawson, A. M. (1974). Jejunal mucosal immunoglobulin-containing cells and jejunal fluid immunoglobulins in adult coeliac disease and dermatitis herpetiformis. Gut 15, 371-376.
86. Lanzavecchia, A. (1985). Antigen-specific interaction between T and B cells. Nature 314, 537-539.
87. Lebreton, C., Menard, S., Abed, J., Cruz-Moura, I., Coppo, R., Dugave, C., et al. (2012). Interactions among secretory immunogloblulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides. Gastroenterology 143, 698-707.
88. Levesque, M. C., Moody, M. A., Hwang, K. K., Marshall, D. J., Whitesides, J. F., Amos, J. D., et al. (2009). Poly-clonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection. PLoS Med. 6, e1000107. doi: 10.1371/journal.pmed.1000107
89. Lindner, C., Wahl, B., Fohse, L., Suer-baum, S., Macpherson, A. J., Prinz, I., et al. (2012). Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. J. Exp. Med. 209, 365-377.
90. Litinskiy, M. B., Nardelli, B., Hilbert, D. M., He, B., Schaffer, A., Casali, P., et al. (2002). DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3, 822-829.
91. Lorand, L., and Graham, R. M. (2003). Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat. Rev. Mol. Cell Biol. 4, 140-156.
92. Lycke, N., Kilander, A., Nilsson, L. A., Tarkowski, A., and Werner, N. (1989). Production of antibodies to gliadin in intestinal mucosa of patients with coeliac disease: a study at the single cell level. Gut 30, 72-77.
93. MacLennan, I. C., Toellner, K. M., Cunningham, A. F., Serre, K., Sze, D. M., Zuniga, E., et al. (2003). Extrafol-licular antibody responses. Immunol. Rev. 194, 8-18.
94. Macpherson, A., Khoo, U. Y., Forgacs, I., Philpott-Howard, J., and Bjarna-son, I. (1996). Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria. Gut 38, 365-375.
95. Macpherson, A. J., Gatto, D., Sainsbury, E., Harriman, G. R., Hengartner, H., and Zinkernagel, R. M. (2000). A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288, 2222-2226.
96. Maki, M., Sulkanen, S., and Collin, P. (1998). Antibodies in relation to gluten intake. Dig. Dis. 16, 330-332.
97. Marietta, E. V., and Murray, J. A. (2012). Animal models to study gluten sensitivity. Semin. Immunopathol. 34, 497-511.
98. Marshall, J. L., Zhang, Y., Pallan, L., Hsu, M. C., Khan, M., Cunningham, A. F., et al. (2011). Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts. Eur. J. Immunol. 41, 3506-3512.
99. Marzari, R., Sblattero, D., Florian, F., Tongiorgi, E., Not, T., Tommasini, A., et al. (2001). Molecular dissection of the tissue transglutaminase autoan-tibody response in celiac disease. J. Immunol. 166, 4170-4176.
100. Matysiak-Budnik, T., Moura, I. C., Arcos-Fajardo, M., Lebreton, C., Menard, S., Candalh, C., et al. (2008). Secretory IgA mediates retrotranscy-tosis of intact gliadin peptides via the transferrin receptor in celiac disease. J. Exp. Med. 205, 143-154.
101. Mayer, M., Greco, L., Troncone, R., Grimaldi, M., and Pansa, G. (1989). Early prediction of relapse during gluten challenge in childhood celiac disease. J. Pediatr. Gastroenterol. Nutr. 8, 474-479.
102. Meresse, B., Malamut, G., and Cerf-Bensussan, N. (2012). Celiac disease: an immunological jigsaw. Immunity 36, 907-919.
103. Mesin, L., Di Niro, R., Thompson, K. M., Lundin, K. E., and Sollid, L. M. (2011). Long-lived plasma cells from human small intestine biopsies secrete immunoglobulins for many weeks in vitro. J. Immunol. 187, 2867-2874.
104. Molberg, O., McAdam, S. N., Korner, R., Quarsten, H., Kristiansen, C., Mad-sen, L., et al. (1998). Tissue transglu-taminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat. Med. 4, 713-717.
105. Mombaerts, P., Mizoguchi, E., Ljung-gren, H. G., Iacomini, J., Ishikawa, H., Wang, L., et al. (1994). Peripheral lymphoid development and function in TCR mutant mice. Int. Immunol. 6, 1061-1070.
106. Mora, J. R., Iwata, M., Eksteen, B., Song, S. Y., Junt, T., Senman, B., et al. (2006). Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314, 1157- 1160.
107. Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y., and Honjo, T. (2000). Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102, 553-563.
108. Myrsky, E., Kaukinen, K., Syrja-nen, M., Korponay-Szabo, I. R., Maki, M., and Lindfors, K. (2008). Coeliac disease-specific autoantibod-ies targeted against transglutaminase 2 disturb angiogenesis. Clin. Exp. Immunol. 152, 111-119.
109. Neutra, M. R. (1999). M cells in antigen sampling in mucosal tissues. Curr. Top. Microbiol. Immunol. 236, 17-32.
110. Neutra, M. R., Mantis, N. J., and Kraehenbuhl, J. P. (2001). Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nat. Immunol. 2, 1004-1009.
111. Ogra, P. L., and Karzon, D. T. (1969). Distribution of poliovirus antibody in serum, nasopharynx and alimentary tract following segmental immunization of lower alimentary tract with poliovaccine. J. Immunol. 102, 1423-1430.
112. Osman, A. A., Richter, T., Stern, M., and Mothes, T. (1996). The IgA subclass distributions of endomysium and gliadin antibodies in human sera are different. Clin. Chim. Acta 255, 145-152.
113. Pabst, O., and Mowat, A. M. (2012). Oral tolerance to food protein. Mucosal Immunol. 5, 232-239.
114. Paparo, F., Petrone, E., Tosco, A., Maglio, M., Borrelli, M., Salvati, V. M., et al. (2005). Clinical, HLA, and small bowel immunohistochem-ical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa. Am. J. Gastroen-terol. 100, 2294-2298.
115. Pelletier, N., McHeyzer-Williams, L. J., Wong, K. A., Urich, E., Fazil-leau, N., and McHeyzer-Williams, M. G. (2010). Plasma cells negatively regulate the follicular helper T cell program. Nat. Immunol. 11, 1110-1118.
116. Radbruch, A., Muehlinghaus, G., Luger, E. O., Inamine, A., Smith, K. G., Dorner, T., et al. (2006). Competence and competition: the challenge of becoming a long-lived plasma cell. Nat. Rev. Immunol. 6, 741-750.
117. Rauhavirta, T., Qiao, S. W., Jiang, Z., Myrsky, E., Loponen, J., Korponay-Szabo, I. R., et al. (2011). Epithelial transport and deamidation of gliadin peptides: a role for coeliac disease patient immunoglobulin A. Clin. Exp. Immunol. 164, 127-136.
118. Reynaud, C. A., Garcia, C., Hein, W. R., and Weill, J. C. (1995). Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process. Cell 80, 115-125.
119. Rimoldi, M., Chieppa, M., Salucci, V., Avogadri, F., Sonzogni, A., Sampi-etro, G. M., et al. (2005). Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat. Immunol. 6, 507-514.
120. Salmi, T. T., Collin, P., Jarvinen, O., Haimila, K., Partanen, J., Laurila, K., et al. (2006a). Immunoglobulin A autoantibodies against transglu-taminase 2 in the small intestinal mucosa predict forthcoming coeliac disease. Aliment. Pharmacol. Ther. 24, 541-552.
121. Salmi, T. T., Collin, P., Korponay-Szabo, I. R., Laurila, K., Partanen, J., Huh-tala, H., et al. (2006b). Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits. Gut 55, 1746- 1753.
122. Sato, A., Hashiguchi, M., Toda, E., Iwasaki, A., Hachimura, S., and Kaminogawa, S. (2003). CD11b+ Peyer's patch dendritic cells secrete IL-6 and induce IgA secretion from naive B cells. J. Immunol. 171, 3684- 3690.
123. Savilahti, E., Viander, M., Perkkio, M., Vainio, E., Kalimo, K., and Reunala, T. (1983). IgA antigliadin antibodies: a marker of mucosal damage in childhood coeliac disease. Lancet 1, 320-322.
124. Sblattero, D., Florian, F., Not, T., Ventura, A., Bradbury, A., and Marzari, R. (2000). Analyzing the peripheral blood antibody repertoire of a celiac disease patient using phage antibody libraries. Hum. Antibodies 9, 199-205.
125. Scheid, J. F., Mouquet, H., Feldhahn, N., Seaman, M. S., Velinzon, K., Piet-zsch, J., et al. (2009). Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636-640.
126. Schumann, M., Richter, J. F., Wedell, I., Moos, V., Zimmermann-Kordmann, M., Schneider, T., et al. (2008). Mechanisms of epithelial translocation of the alpha(2)-gliadin-33mer in coeliac sprue. Gut 57, 747-754.
127. Scott, H., Ek, J., Baklien, K., and Brandtzaeg, P. (1980). Immuno-globulin-producing cells in jejunal mucosa of children with coeliac disease on a gluten-free diet and after gluten challenge. Scand. J. Gastroen-terol. 15, 81-88.
128. Shih, T. A., Meffre, E., Roederer, M., and Nussenzweig, M. C. (2002). Role of BCR affinity in T cell dependent antibody responses in vivo. Nat. Immunol. 3, 570-575.
129. Shikina, T., Hiroi, T., Iwatani, K., Jang, M. H., Fukuyama, S., Tamura, M., et al. (2004). IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut. J. Immunol. 172, 6259-6264.
130. Shiner, M., and Ballard, J. (1972). Antigen-antibody reactions in jeju-nal mucosa in childhood coeliac disease after gluten challenge. Lancet 1, 1202-1205.
131. Sollid, L. M. (2002). Coeliac disease: dissecting a complex inflammatory disorder. Nat. Rev. Immunol. 2, 647-655.
132. Sollid, L. M., Molberg, O., McAdam, S., and Lundin, K. E. (1997). Autoanti-bodies in coeliac disease: tissue trans-glutaminase - guilt by association? Gut 41, 851-852.
133. Sollid, L. M., Qiao, S. W., Anderson, R. P., Gianfrani, C., and Koning, F. (2012). Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics 64, 455-460.
134. Soltoft, J. (1970). Immunoglobulin-containing cells in non-tropical sprue. Clin. Exp. Immunol. 6, 413-420.
135. Spencer, J., Klavinskis, L. S., and Fraser, L. D. (2012). The human intestinal IgA response; burning questions. Front. Immunol. 3:108. doi: 10.3389/fimmu.2012.00108
136. Stavnezer, J., and Kang, J. (2009). The surprising discovery that TGF beta specifically induces the IgA class switch. J. Immunol. 182, 5-7.
137. Stern, M., and Dietrich, R. (1982). Gliadin- and immunoglobulin-containing cells of small intestinal lamina propria in childhood coeliac disease. Eur. J. Pediatr. 139, 13-17.
138. Strugnell, R. A., and Wijburg, O. L. (2010). The role of secretory antibodies in infection immunity. Nat. Rev. Microbiol. 8, 656-667.
139. Su, W., Gordon, J. N., Barone, F., Bour-sier, L., Turnbull, W., Mendis, S., et al. (2008). Lambda light chain revision in the human intestinal IgA response. J. Immunol. 181, 1264-1271.
140. Sulkanen, S., Halttunen, T., Laurila, K., Kolho, K. L., Korponay-Szabo, I. R., Sarnesto, A., et al. (1998). Tissue transglutaminase autoanti-body enzyme-linked immunosor-bent assay in detecting celiac disease. Gastroenterology 115, 1322-1328.
141. Tezuka, H., Abe, Y., Iwata, M., Takeuchi, H., Ishikawa, H., Matsushita, M., et al. (2007). Regulation of IgA productionbynaturally occurring TNF/iNOS-producing dendritic cells. Nature 448, 929-933.
142. Toellner, K. M., Jenkinson,W. E., Taylor, D. R., Khan, M., Sze, D. M., San-som, D. M., et al. (2002). Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers. J. Exp. Med. 195, 383-389.
143. Tosco, A., Maglio, M., Paparo, F., Rapacciuolo, L., Sannino, A., Miele, E., et al. (2008). Immunoglobu-lin A anti-tissue transglutaminase antibody deposits in the small intestinal mucosa of children with no vil-lous atrophy. J. Pediatr. Gastroenterol. Nutr. 47, 293-298.
144. Toyama, H., Okada, S., Hatano, M., Takahashi, Y., Takeda, N., Ichii, H., et al. (2002). Memory B cells without somatic hypermutation are generated from Bcl6-deficient B cells. Immunity 17, 329-339.
145. Tursi, A., Brandimarte, G., and Gior-getti, G. M. (2003). Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. J. Clin. Gastroenterol. 36, 219-221.
146. Valletta, E. A., Trevisiol, D., and Mas-tella, G. (1990). IgA anti-gliadin antibodies in the monitoring of gluten challenge in celiac disease. J. Pediatr. Gastroenterol. Nutr. 10, 169-173.
147. van de Wal, Y., Kooy, Y., Van Veelen, P., Pena, S., Mearin, L., Papadopoulos, G., et al. (1998). Selective deami-dation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J. Immunol. 161, 1585- 1588.
148. Victor, K. D., Randen, I., Thompson, K., Forre, O., Natvig, J. B., Fu, S. M., et al. (1991). Rheumatoid factors isolated from patients with autoimmune disorders are derived from germline genes distinct from those encoding the Wa, Po, and Bla cross-reactive idiotypes. J. Clin. Invest. 87, 1603- 1613.
149. Victora, G. D., and Nussenzweig, M. C. (2012). Germinal centers. Annu. Rev. Immunol. 30, 429-457.
150. Wei, M., Shinkura, R., Doi, Y., Maruya, M., Fagarasan, S., and Honjo, T. (2011). Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nat. Immunol. 12, 264-270.
151. Weiner, H. L., Da Cunha, A. P., Quintana, F., and Wu, H. (2011). Oral tolerance. Immunol. Rev. 241, 241-259.
152. Weitkamp, J. H., Kallewaard, N., Kusuhara, K., Bures, E., Williams, J. V., Lafleur, B., et al. (2003). Infant and adult human B cell responses to rotavirus share common immun-odominant variable gene repertoires. J. Immunol. 171, 4680-4688.
153. William, J., Euler, C., Christensen, S., and Shlomchik, M. J. (2002). Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 297, 2066- 2070.
154. Wood, G. M., Howdle, P. D., Trej-dosiewicz, L. K., and Losowsky, M. S. (1987). Jejunal plasma cells and in vitro immunoglobulin production in adult coeliac disease. Clin. Exp. Immunol. 69, 123-132.
155. Wrammert, J., Smith, K., Miller, J., Lan-gley, W. A., Kokko, K., Larsen, C., et al. (2008). Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 453, 667-671.
156. Yuvaraj, S., Dijkstra, G., Burgerhof, J. G., Dammers, P. M., Stoel, M., Visser, A., et al. (2009). Evidence for local expansion of IgA plasma cell precursors in human ileum. J. Immunol. 183, 4871-4878.