Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis

Annual Review of Immunology

Volumn 28, Issue , 2010, Pages 243-273

  Fagarasan, Sidonia ^a   Kawamoto, Shimpei ^a,b   Kanagawa, Osami ^a   Suzuki, Keiichiro ^a  

^a RIKEN   (Japan)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

Activation induced cytidine deaminase (AID); Bacteria; Dendritic cells; Follicular T helper cells; Peyer's patches

Indexed keywords

B LYMPHOCYTE RECEPTOR; GAMMA INTERFERON; IMMUNOGLOBULIN A; INTERLEUKIN 17; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RECEPTOR;

ADAPTIVE IMMUNITY; ANTIGEN RECOGNITION; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; BACTERIUM; CELLULAR IMMUNITY; GERMINAL CENTER; HOMEOSTASIS; HUMAN; IMMUNIZATION; IMMUNOGLOBULIN PRODUCTION; IMMUNOREGULATION; INTESTINE; INTESTINE FLORA; LAMINA PROPRIA; LYMPH FOLLICLE; LYMPHOID CELL; MICROBIAL COMMUNITY; NONHUMAN; PEYER PATCH; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; ANIMAL; ANTIBODY PRODUCTION; BIOSYNTHESIS; GASTROINTESTINAL TRACT; IMMUNOLOGY;

ADAPTIVE IMMUNITY; ANIMALS; ANTIBODY FORMATION; GASTROINTESTINAL TRACT; HOMEOSTASIS; HUMANS; IMMUNOGLOBULIN A; T-LYMPHOCYTES;

EID: 77952311371     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev-immunol-030409-101314     Document Type: Review

References (231)

1. Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. 2008. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat. Rev. Microbiol. 6:776-788
2. Hooper LV, Gordon JI. 2001. Commensal host-bacterial relationships in the gut. Science 292:1115-1118
3. Noverr MC, Huffnagle GB. 2004. Does the microbiota regulate immune responses outside the gut? Trends Microbiol. 12:562-568
4. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, et al. 2005. Diversity of the human intestinal microbial flora. Science 308:1635-1638
5. Mahowald MA, Rey FE, Seedorf H, Turnbaugh PJ, Fulton RS, et al. 2009. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla. Proc. Natl. Acad. Sci. USA 106:5859-5864
6. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. 2005. Host-bacterial mutualism in the human intestine. Science 307:1915-1920
7. Stappenbeck TS, Hooper LV, Gordon JI. 2002. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc. Natl. Acad. Sci. USA 99:15451-15455
8. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. 2004. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118:229-241
9. Sonnenburg JL, Angenent LT, Gordon JI. 2004. Getting a grip on things: How do communities of bacterial symbionts become established in our intestine? Nat. Immunol. 5:569-573
10. Macpherson AJ, Mc Coy KD, Johansen FE, Brandtzaeg P. 2008. The immunegeographyofIgA induction and function. Mucosal Immunol. 1:11-22
11. Loker ES, Adema CM, Zhang SM, Kepler TB. 2004. Invertebrate immune systems\not homogeneous, not simple, not well understood. Immunol. Rev. 198:10-24
12. Flajnik MF, Du Pasquier L.2004. Evolution of innate and adaptive immunity: Can we draw a line? Trends Immunol. 25:640-644
13. Rakoff-Nahoum S, Medzhitov R. 2008. Innate immune recognition of the indigenous microbial flora. Mucosal Immunol. 1(Suppl. 1):S10-14
14. Pancer Z, Cooper MD. 2006. The evolution of adaptive immunity. Annu. Rev. Immunol. 24:497-518
15. Guo P, Hirano M, Herrin BR, Li J, Yu C, et al. 2009. Dual nature of the adaptive immune system in lampreys. Nature 459:796-801
16. Rogozin IB, Iyer LM, Liang L, Glazko GV, Liston VG, et al. 2007. Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase. Nat. Immunol. 8:647-656
17. Matsunaga T, Rahman A. 1998. What brought the adaptive immune system to vertebrates?\The jaw hypothesis and the seahorse. Immunol. Rev. 166:177-186
18. Matsunaga T, Rahman A. 2001. In search of the origin of the thymus: The thymus and GALT may be evolutionarily related. Scand. J. Immunol. 53:1-6
19. Peppard JV, Kaetzel CS, Russell MW. 2005. Phylogeny and comparative physiology of IgA. In Mucosal Immunology, ed. J Mestecky, M Lamm, J McGhee, J Bienenstock, L Mayer, W Strobel, pp. 195-210. San Diego: Academic
20. Van Der Heijden PJ, Stok W, Bianchi AT. 1987. Contribution of immunoglobulin-secreting cells in the murine small intestine to the total 'background' immunoglobulin production. Immunology 62:551-555
21. Van Egmond M, Damen CA, Van Spriel AB, Vidarsson G, Van Garderen E, Van De Winkel JG. 2001. IgA and the IgA Fc receptor. Trends Immunol. 22:205-211
22. Mostov KE. 1994. Transepithelial transport of immunoglobulins. Annu. Rev. Immunol. 12:63-84
23. Brandtzaeg P, Baekkevold ES, Farstad IN, Jahnsen FL, Johansen FE, et al. 1999. Regional specialization in the mucosal immune system: What happens in the microcompartments? Immunol. Today 20:141-151 (Pubitemid 29130344)
24. Jung D, Giallourakis C, Mostoslavsky R, Alt FW. 2006. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu. Rev. Immunol. 24:541-570
25. Honjo T, Kinoshita K, Muramatsu M. 2002. Molecular mechanism ofclass switch recombination: linkage with somatic hypermutation. Annu. Rev. Immunol. 20:165-196
26. Chaudhuri J, Basu U, Zarrin A, Yan C, Franco S, et al. 2007. Evolution of the immunoglobulin heavy chain class switch recombination mechanism. Adv. Immunol. 94:157-214
27. Muramatsu M, Nagaoka H, Shinkura R, Begum NA, Honjo T. 2007. Discovery of activation-induced cytidine deaminase, the engraver of antibody memory. Adv. Immunol. 94:1-36
28. Honjo T, Kataoka T. 1978. Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc. Natl. Acad. Sci. USA 75:2140-2144
29. Chen K, Xu W, Wilson M, He B, Miller NW, et al. 2009. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat. Immunol. 10:889-898
30. Vladutiu AO. 2000. Immunoglobulin D: properties, measurement, and clinical relevance. Clin. Diagn. Lab. Immunol. 7:131-140
31. Nikaido T, Nakai S, Honjo T. 1981. Switch region of immunoglobulin Cmu gene is composed of simple tandem repetitive sequences. Nature 292:845-848
32. Strobel W, Fagarasan S, Lycke N. 2005. IgA B cell development. In Mucosal Immunology, ed. J Mestecky, M Lamm, J McGhee, J Bienenstock, L Mayer, W Strobel, pp. 583-616. San Diego: Academic
33. Goodman MF, Scharff MD, Romesberg FE. 2007. AID-initiated purposeful mutations in immunoglob-ulin genes. Adv. Immunol. 94:127-155
34. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. 2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553-563
35. Revy P, Muto T, Levy Y, Geissmann F, Plebani A, et al. 2000. Activation-induced cytidine deami-nase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102:565-575
36. Arakawa H, Hauschild J, Buerstedde JM. 2002. Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion. Science 295:1301-1306
37. Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, et al. 1999. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J. Biol. Chem. 274:18470-18476
38. Honjo T. 2008. A memoir of AID, which engraves antibody memory on DNA. Nat. Immunol. 9:335-337
39. Conticello SG, Thomas CJ, Petersen-Mahrt SK, Neuberger MS. 2005. Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases. Mol. Biol. Evol. 22:367-377
40. Cannon JP, Haire RN, Rast JP, Litman GW. 2004. The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms. Immunol. Rev. 200:12-22
41. Barreto VM, Pan-Hammarstrom Q, Zhao Y, Hammarstrom L, Misulovin Z, Nussenzweig MC. 2005. AID from bony fish catalyzes class switch recombination. J. Exp. Med. 202:733-738
42. Wakae K, Magor BG, Saunders H, Nagaoka H, Kawamura A, et al. 2006. Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID. Int. Immunol. 18:41-47
43. Flajnik MF. 2002. Comparative analyses of immunoglobulin genes: surprises and portents. Nat. Rev. Immunol. 2:688-698
44. Mussmann R, Courtet M, Schwager J, Du Pasquier L. 1997. Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals. Eur. J. Immunol. 27:2610-2619
45. Marr S, Morales H, Bottaro A, Cooper M, Flajnik M, Robert J. 2007. Localization and differential expression of activation-induced cytidine deaminase in the amphibian Xenopus upon antigen stimulation and during early development. J. Immunol. 179:6783-6789
46. Braathen R, Hohman VS, Brandtzaeg P, Johansen FE. 2007. Secretory antibody formation: conserved binding interactions betweenJ chain and polymeric Ig receptor from humans and amphibians. J. Immunol. 178:1589-1597
47. Nishikawa SI, Hashi H, Honda K, Fraser S, Yoshida H. 2000. Inflammation, a prototype for organogenesis of the lymphopoietic/hematopoietic system. Curr. Opin. Immunol. 12:342-345
48. Mebius RE. 2003. Organogenesis of lymphoid tissues. Nat. Rev. Immunol. 3:292-303
49. Finke D, Meier D. 2006. Molecular networks orchestrating GALT development. Curr. Top. Microbiol. Immunol. 308:19-57
50. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, et al. 1999. Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702-706
51. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR. 2004. An essential function for the nuclear receptor RORy(t) in the generation of fet al lymphoid tissue inducer cells. Nat. Immunol. 5:64-73
52. Yoshida H, Honda K, Shinkura R, Adachi S, Nishikawa S, et al. 1999. IL-7 receptor a+ CD3-cells in the embryonic intestine induces the organizing center of Peyer's patches. Int. Immunol. 11:643-655
53. Mebius RE, Streeter PR, Michie S, Butcher EC, Weissman IL. 1996. A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+ CD3-cells to colonize lymph nodes. Proc. Natl. Acad. Sci. USA 93:11019-11024
54. +CD3-cells induce Peyer's patch development: role of a4|31 integrin activation by CXCR5. Immunity 17:363-373
55. Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM, et al. 2002. Different cytokines induce surface lymphotoxin-a|3 on IL-7 receptor-a cells that differentially engender lymph nodes and Peyer's patches. Immunity 17:823-833
56. Meier D, Bornmann C, Chappaz S, Schmutz S, Otten LA, et al. 2007. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26:643-654
57. Dejardin E, Droin NM, Delhase M, Haas E, Cao Y, et al. 2002. The lymphotoxin-13 receptor induces different patterns of gene expression via two NF-KB pathways. Immunity 17:525-535
58. Gommerman JL, Browning JL. 2003. Lymphotoxin/light, lymphoid microenvironments and autoimmune disease. Nat. Rev. Immunol. 3:642-655
59. Allen CD, Cyster JG 2008. Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function. Semin. Immunol. 20:14-25
60. Allen CD, Okada T, Cyster JG. 2007. Germinal-center organization and cellular dynamics. Immunity 27:190-202
61. Klein U, Dalla-Favera R 2008. Germinal centres: role in B-cell physiology and malignancy. Nat. Rev. Immunol. 8:22-33
62. Basso K, Sumazin P, Morozov P, Schneider C, Maute RL, et al. 2009. Identification of the human mature B cell miRNome. Immunity 30:744-752
63. Xiao C, Rajewsky K. 2009. MicroRNA control in the immune system: basic principles. Cell 136:26-36
64. Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, et al. 2007. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131:146-159
65. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, et al. 2007. Requirement of bic/microRNA-155 for normal immune function. Science 316:608-611
66. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, et al. 2007. Regulation of the germinal center response by microRNA-155. Science 316:604-608
67. TengG, HakimpourP, Landgraf P, Rice A, Tuschl T, et al. 2008. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28:621-629
68. Dorsett Y, McBride KM, Jankovic M, Gazumyan A, Thai TH, et al. 2008. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 28:630-638
69. Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T. 2002. Critical roles of activation-induced cytidine deaminase (AID) in the homeostasis of gut flora. Science 298:1424-1427
70. Cebra JJ. 1999. Influences of microbiota on intestinal immune system development. Am. J. Clin. Nutr. 69:S1046-51
71. Casola S, Otipoby KL, Alimzhanov M, Humme S, Uyttersprot N, et al. 2004. B cell receptor signal strength determines B cell fate. Nat. Immunol. 5:317-327
72. Casola S, Rajewsky K. 2006. B cell recruitment and selection in mouse GALT germinal centers. Curr. Top. Microbiol. Immunol. 308:155-171
73. Pasare C, Medzhitov R. 2005. Control of B-cell responses by Toll-like receptors. Nature 438:364-368
74. Gavin AL, Hoebe K, Duong B, Ota T, Martin C, et al. 2006. Adjuvant-enhanced antibody responses in the absence of Toll-like receptor signaling. Science 314:1936-1938
75. Meyer-Bahlburg A, Khim S, Rawlings DJ. 2007. B cell intrinsic TLR signals amplify but are not required for humoral immunity. J. Exp. Med. 204:3095-3101
76. Wen L, Pao W, Wong FS, Peng Q, Craft J, et al. 1996. Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non α/β" T cells. J. Exp. Med. 183:2271-2282
77. Dianda L, Gulbranson-Judge A, Pao W, Hayday AC, MacLennan IC, Owen MJ. 1996. Germinal center formation in mice lacking αβ T cells. Eur. J. Immunol. 26:1603-1607
78. Vinuesa CG, Tangye SG, Moser B, Mackay CR. 2005. Follicular B helper T cells in antibody responses and autoimmunity. Nat. Rev. Immunol. 5:853-865
79. Walker LS, Gulbranson-Judge A, Flynn S, Brocker T, Raykundalia C, et al. 1999. Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers. J. Exp. Med. 190:1115-1122
80. Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. 2000. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J. Exp. Med. 192:1553-1562
81. Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, et al. 2000. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J. Exp. Med. 192:1545-1552
82. high germinal center-associated subpopulation. J. Immunol. 179:5099-5108
83. + T cells to follicular DC. Eur. J. Immunol. 39:695-703
84. Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L, et al. 2005. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435:452-458
85. Reinhardt RL, Liang HE, Locksley RM. 2009. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat. Immunol. 10:385-393
86. Hardtke S, Ohl L, Forster R. 2005. Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help. Blood 106:1924-1931
87. Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, et al. 2008. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29:138-149
88. Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C. 2008. A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 29:127-137
89. + T cell development and humoral immunity is independent of SLAM and Fyn kinase. J. Immunol. 178:817-828
90. Qi H, Cannons JL, Klauschen F, Schwartzberg PL, Germain RN. 2008. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455:764-769
91. Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, et al. 2009. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325:1006-1010
92. Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, et al. 2009. Bcl6 mediates the development of T follicular helper cells. Science 325:1001-1005
93. Yu D, Rao S, Tsai LM, Lee SK, He Y, et al. 2009. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31:457-468
94. Fazilleau N, McHeyzer-Williams LJ, Rosen H, McHeyzer-Williams MG. 2009. The function of fol-licular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat. Immunol. 10:375-384
95. + T cells in gut Peyer's patches. Science 323:1488-1492
96. Lim HW, Hillsamer P, Kim CH. 2004. Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses. J. Clin. Invest. 114:1640-1649
97. + regulatory T cells. J. Immunol. 175:4180-4183
98. + T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J. Exp. Med. 206:1001-1007
99. Zaretsky AG, Taylor JJ, King IL, Marshall FA, Mohrs M, Pearce EJ. 2009. T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J. Exp. Med. 206:991-999
100. Belkaid Y, Tarbell K. 2009. Regulatory T cells in the control of host-microorganism interactions. Annu. Rev. Immunol. 27:551-589
101. Duarte JH, Zelenay S, Bergman ML, Martins AC, Demengeot J. 2009. Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 39:948-955
102. + T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc. Natl. Acad. Sci. USA 106:1903-1908
103. Zhou X, Bailey-Bucktrout S, Jeker LT, Penaranda C, Martinez-Llordella M, et al. 2009. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat. Immunol. 10:1000-1007
104. Craig SW, Cebra JJ. 1971. Peyer's patches: an enriched source of precursors for IgA-producing immuno-cytes in the rabbit. J. Exp. Med. 134:188-200
105. Craig SW, Cebra JJ. 1975. Rabbit Peyer's patches, appendix, and popliteal lymph node B lymphocytes: a comparative analysis of their membrane immunoglobulin components and plasma cell precursor potential. J. Immunol. 114:492-502
106. Butcher EC, Rouse RV, Coffman RL, Nottenburg CN, Hardy RR, Weissman IL. 1982. Surface phe-notype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation. J. Immunol. 129:2698-2707
107. Cerutti A, Rescigno M. 2008. The biology of intestinal immunoglobulin A responses. Immunity 28:740-750
108. Suzuki K, Fagarasan S. 2008. How host-bacterial interactions lead to IgA synthesis in the gut. Trends Immunol. 29:523-531
109. Sonoda E, Matsumoto R, Hitoshi Y, Ishii T, Sugimoto M, et al. 1989. Transforming growth factor β induces IgA production and acts additively with interleukin 5 for IgA production. J. Exp. Med. 170:1415-1420
110. Cazac BB, Roes J. 2000. TGF-β receptor controls B cell responsiveness and induction of IgA in vivo. Immunity 13:443-451
111. Fink LN, Frokiaer H. 2008. Dendritic cells from Peyer's patches and mesenteric lymph nodes differ from spleen dendritic cells in their response to commensal gut bacteria. Scand. J. Immunol. 68:270-279
112. Annes JP, Munger JS, Rifkin DB. 2003. Making sense of latent TGFβ activation. J. Cell Sci. 116:217-224
113. Dullaers M, Li D, Xue Y, Ni L, Gayet I, et al. 2009. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. Immunity 30:120-129
114. Avery DT, Bryant VL, Ma CS, de Waal Malefyt R, Tangye SG. 2008. IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4. J. Immunol. 181:1767-1779
115. Kadaoui KA, Corthesy B. 2007. Secretory IgA mediates bacterial translocation to dendritic cells in mouse Peyer's patches with restriction to mucosal compartment. J. Immunol. 179:7751-7757
116. Rey J, Garin N, Spertini F, Corthesy B. 2004. Targeting of secretory IgA to Peyer's patch dendritic and T cells after transport by intestinal M cells. J. Immunol. 172:3026-3033
117. Neutra MR, Mantis NJ, Kraehenbuhl JP. 2001. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nat. Immunol. 2:1004-1009
118. Sato A, Hashiguchi M, Toda E, Iwasaki A, Hachimura S, 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
119. Mora JR, Iwata M, Eksteen B, Song SY, Junt T, et al. 2006. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314:1157-1160
120. Pabst O, Ohl L, Wendland M, Wurbel MA, Kremmer E, et al. 2004. Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine. J. Exp. Med. 199:411-416
121. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. 2004. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21:527-538
122. Gohda M, Kunisawa J, Miura F, Kagiyama Y, Kurashima Y, et al. 2008. Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responses. J. Immunol. 180:5335-5343
123. + Thy1+ lympho-hemopoietic progenitors develop. J. Exp. Med. 184:1449-1459
124. + cells. Science 305:248-251
125. Naito T, Shiohara T, Hibi T, Suematsu M, Ishikawa H. 2008. RORyt is dispensable for the development of intestinal mucosal T cells. Mucosal Immunol. 1:198-207
126. Saito H, Kanamori Y, Takemori T, Nariuchi H, Kubota E, et al. 1998. Generation of intestinal T cells from progenitors residing in gut cryptopatches. Science 280:275-278
127. Suzuki K, Oida T, Hamada H, Hitotsumatsu O, Watanabe M, et al. 2000. Gut cryptopatches: direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis. Immunity 13:691-702
128. Hayday A, Gibbons D. 2008. Brokering the peace: the origin of intestinal T cells. Mucosal Immunol. 1:172-174
129. + T helper cells. Cell 126:1121-1133
130. Ivanov, II, Diehl GE, Littman DR. 2006. Lymphoid tissue inducer cells in intestinal immunity. Curr. Top. Microbiol. Immunol. 308:59-82
131. Fagarasan S. 2006. Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut. Curr. Top. Microbiol. Immunol. 308:137-153
132. Newberry RD, McDonough JS, McDonald KG, Lorenz RG 2002. Postgestational lymphotoxin/lymphotoxin |3 receptor interactions are essential for the presence of intestinal B lymphocytes. J. Immunol. 168:4988-4997
133. Pabst O, Herbrand H, Worbs T, Friedrichsen M, Yan S, et al. 2005. Cryptopatches and isolated lymphoid follicles: dynamic lymphoid tissues dispensable for the generation of intraepithelial lymphocytes. Eur. J. Immunol. 35:98-107
134. Pabst O, Herbrand H, Friedrichsen M, Velaga S, Dorsch M, et al. 2006. Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling. J. Immunol. 177:6824-6832
135. Moghaddami M, Cummins A, Mayrhofer G 1998. Lymphocyte-filled villi: comparison with other lymphoid aggregations in the mucosa of the human small intestine. Gastroenterology 115:1414-1425
136. Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, et al. 2002. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J. Immunol. 168:57-64
137. Lorenz RG, Chaplin DD, McDonald KG, McDonough JS, Newberry RD. 2003. Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin P receptor, and TNF receptor I function. J. Immunol. 170:5475-5482
138. McDonald KG, McDonough JS, Newberry RD. 2005. Adaptive immune responses are dispensable for isolated lymphoid follicle formation: Antigen-naive, lymphotoxin-sufficient B lymphocytes drive the formation of mature isolated lymphoid follicles. J. Immunol. 174:5720-5728
139. Taylor RT, Lugering A, Newell KA, Williams IR. 2004. Intestinal cryptopatch formation in mice requires lymphotoxin a and the lymphotoxin |3 receptor. J. Immunol. 173:7183-7189
140. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, et al. 1999. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-Kb-inducing kinase. Nat. Genet. 22:74-77
141. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, et al. 2008. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 29:261-271
142. McDonald KG, McDonough JS, Wang C, Kucharzik T, Williams IR, Newberry RD. 2007. CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles. Am. J. Pathol. 170:1229-1240
143. Wang C, McDonough JS, McDonald KG, Huang C, Newberry RD. 2008. a4|37/MAdCAM-1 interactions play an essential role in transitioning cryptopatches into isolated lymphoid follicles and a nonessential role in cryptopatch formation. J. Immunol. 181:4052-4061
144. Velaga S, Herbrand H, Friedrichsen M, Jiong T, Dorsch M, et al. 2009. Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J. Immunol. 182:2610-2619
145. Bouskra D, Brezillon C, Berard M, Werts C, Varona R, et al. 2008. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456:507-510
146. Kim MY, Toellner KM, White A, McConnell FM, Gaspal FM, et al. 2006. Neonatal and adult CD4+CD3-cells share similar gene expression profile, and neonatal cells up-regulate OX40 ligand in response to TL1A (TNFSF15). J. Immunol. 177:3074-3081
147. Taylor RT, Patel SR, Lin E, Butler BR, Lake JG, et al. 2007. Lymphotoxin-independent expression of TNF-related activation-induced cytokine by stromal cells in cryptopatches, isolated lymphoid follicles, and Peyer's patches. J. Immunol. 178:5659-5667
148. Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, et al. 2009. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med. 206:35-41
149. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, et al. 2008. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14:282-289
150. Vivier E, Spits H, Cupedo T. 2009. Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair? Nat. Rev. Immunol. 9:229-234
151. Yamamoto M, Rennert P, McGhee JR, Kweon MN, Yamamoto S, et al. 2000. Alternate mucosal immune system: Organized Peyer's patches are not required for IgA responses in the gastrointestinal tract. J. Immunol. 164:5184-5191
152. Martinoli C, Chiavelli A, Rescigno M. 2007. Entry route of Salmonella typhimurium directs the type of induced immune response. Immunity 27:975-984
153. Halle S, Bumann D, Herbrand H, Willer Y, Dahne S, et al. 2007. Solitary intestinal lymphoid tissue provides a productive port of entry for Salmonella enterica serovar Typhimurium. Infect. Immun. 75:1577-1585
154. Niess JH, Brand S, Gu X, Landsman L, Jung S, et al. 2005. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254-258
155. Tezuka H, Abe Y, Iwata M, Takeuchi H, Ishikawa H, et al. 2007. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature 448:929-933
156. HeidingerM, Kolb H, Krell HW, Jochum M, Ries C. 2006. Modulation of autocrine TNF-a-stimulated matrix met alloproteinase 9 (MMP-9) expression by mitogen-activated protein kinases in THP-1 monocytic cells. Biol. Chem. 387:69-78
157. Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, et al. 2002. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat. Immunol. 3:822-829
158. He B, Raab-Traub N, Casali P, Cerutti A. 2003. EBV-encoded latent membrane protein 1 cooperates with BAFF/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching. J. Immunol. 171:5215-5224
159. He B, Xu W, Santini PA, Polydorides AD, Chiu A, et al. 2007. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 26:812-826
160. Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, et al. 2008. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat. Immunol. 9:769-776
161. Fagarasan S, Kinoshita K, Muramatsu M, Ikuta K, Honjo T. 2001. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413:639-643
162. Kinoshita K, Harigai M, Fagarasan S, Muramatsu M, Honjo T. 2001. A hallmark of active class switch recombination: transcripts directed by I promoters on looped-out circular DNAs. Proc. Natl. Acad. Sci. USA 98:12620-12623
163. Shikina T, Hiroi T, Iwatani K, JangMH, Fukuyama S, 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
164. Bergqvist P, Gardby E, Stensson A, BemarkM, Lycke NY. 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
165. Crouch EE, Li Z, Takizawa M, Fichtner-Feigl S, Gourzi P, et al. 2007. Regulation of AID expression in the immune response. J. Exp. Med. 204:1145-1156
166. Shang L, Fukata M, Thirunarayanan N, Martin AP, Arnaboldi P, et al.2008. Toll-like receptor signaling in small intestinal epithelium promotes B-cell recruitment and IgA production in lamina propria. Gastroenterology 135:529-538
167. Suzuki K, Meek B, Doi Y, Honjo T, Fagarasan S. 2005. Two distinctive pathways for recruitment of naive and primed IgM+ B cells to the gut lamina propria. Proc. Natl. Acad. Sci. USA 102:2482-2486
168. Velazquez P, Wei B, McPherson M, Mendoza LM, Nguyen SL, et al. 2008. Villous B cells of the small intestine are specialized for invariant NKT cell dependence. J. Immunol. 180:4629-4638
169. Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM. 2000. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288:2222-2226
170. Shimomura Y, Ogawa A, Kawada M, Sugimoto K, Mizoguchi E, et al. 2008. A unique B2 B cell subset in the intestine. J. Exp. Med. 205:1343-1355
171. Kang HS, Chin RK, Wang Y, Yu P, Wang J, et al. 2002. Signaling via LT|3R on the lamina propria stromal cells of the gut is required for IgA production. Nat. Immunol. 3:576-582
172. Fagarasan S, Shinkura R, Kamata T, Nogaki F, Ikuta K, et al. 2000. Alymphoplasia (aly)-type nuclear factor KB-inducing kinase (NIK) causes defects in secondary lymphoid tissue chemokine receptor signaling and homing of peritoneal cells to the gut-associated lymphatic tissue system. J. Exp. Med. 191:1477-1486
173. Martin F, Kearney JF. 2001. B1 cells: similarities and differences with other B cell subsets. Curr. Opin. Immunol. 13:195-201
174. Herzenberg LA, Tung JW. 2006. B cell lineages: documented at last! Nat. Immunol. 7:225-226
175. Ha SA, Tsuji M, Suzuki K, Meek B, Yasuda N, Kaisho T, Fagarasan S. 2006. Regulation of B1 cell migration by signals through Toll-like receptors. J. Exp. Med. 203:2541-2550
176. Won WJ, Kearney JF. 2002. CD9 is a unique marker for marginal zone B cells, B1 cells, and plasma cells in mice. J. Immunol. 168:5605-5611
177. Berberich S, Forster R, Pabst O. 2007. The peritoneal micromilieu commits
178. Kunisawa J, Kurashima Y, Gohda M, Higuchi M, Ishikawa I, et al. 2007. Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production. Blood 109:3749-3756
179. Sun CM, Hall JA, Blank RB, BouladouxN, OukkaM, et al. 2007. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 204:1775-1785
180. + regulatory T cells via a TGF-|3 and retinoic acid-dependent mechanism. J. Exp. Med. 204:1757-1764
181. Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ. 2007. All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J. Exp. Med. 204:1765-1774
182. + RORy t+ T cells. J. Exp. Med. 205:1381-1393
183. + T cell lineage differentiation. Immunity 30:646-655
184. Min B, Thornton A, Caucheteux SM, Younes SA, Oh K, et al. 2007. Gut flora antigens are not important in the maintenance of regulatory T cell heterogeneity and homeostasis. Eur. J. Immunol. 37:1916-1923
185. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, et al. 2007. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256-260
186. Hall JA, Bouladoux N, Sun CM, Wohlfert EA, Blank RB, et al. 2008. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity 29:637-649
187. Ivanov II, de Lanos Frutos R, Manel N, Yoshinaga K, Rifkin DB, et al. 2008. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4:337-349
188. Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, et al. 2003. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164-169
189. Belkaid Y, Oldenhove G. 2008. Tuning microenvironments: induction of regulatory T cells by dendritic cells. Immunity 29:362-371
190. + T cells. Curr. Opin. Immunol. 21:281-285
191. + regulatory T cells: differentiation, specification, subphenotypes. Nat. Immunol. 10:689-695
192. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R, et al. 2008. TGF-β-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORγt function. Nature 453:236-240
193. + T cells during cure of colitis. J. Immunol. 177:5852-5860
194. Rubtsov YP, Rasmussen JP, Chi EY, Fontenot J, Castelli L, et al. 2008. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28:546-558
195. Li MO, Wan YY, Flavell RA. 2007. T cell-produced transforming growth factor-β1 controls T cell tolerance and regulates Th1-and Th17-cell differentiation. Immunity 26:579-591
196. Izcue A, Coombes JL, Powrie F. 2009. Regulatory lymphocytes and intestinal inflammation. Annu. Rev. Immunol. 27:313-338
197. Jaffar Z, Ferrini ME, Herritt LA, Roberts K. 2009. Cutting edge: Lung mucosal Th17-mediated responses induce polymeric Ig receptor expression by the airway epithelium and elevate secretory IgA levels. J. Immunol. 182:4507-4511
198. Terahara K, Yoshida M, Igarashi O, Nochi T, Pontes GS, et al. 2008. Comprehensive gene expression profilingofPeyer's patch Mcells, villous M-like cells, and intestinal epithelial cells. J. Immunol. 180:7840-7846
199. Jang MH, Kweon MN, Iwatani K, Yamamoto M, Terahara K, et al. 2004. Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc. Natl. Acad. Sci. USA 101:6110-6115
200. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, et al. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2:361-367
201. Chieppa M, Rescigno M, Huang AY, Germain RN. 2006. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203:2841-2852
202. Vallon-Eberhard A, Landsman L, Yogev N, Verrier B, Jung S. 2006. Transepithelial pathogen uptake into the small intestinal lamina propria. J. Immunol. 176:2465-2469
203. Fagarasan S, Honjo T. 2003. Intestinal IgA synthesis: regulation of front-line body defences. Nat. Rev. Immunol. 3:63-72
204. Castigli E, Wilson SA, Scott S, Dedeoglu F, Xu S, et al. 2005. TACI and BAFF-R mediate isotype switching in B cells. J. Exp. Med. 201:35-39
205. Sakurai D, Hase H, Kanno Y, Kojima H, Okumura K, Kobata T. 2007. TACI regulates IgA production by APRIL in collaboration with HSPG. Blood 109:2961-2967
206. Iliev ID, Mileti E, Matteoli G, Chieppa M, Rescigno M. 2009. Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol. 2:340-350
207. Taylor BC, Zaph C, Troy AE, Du Y, Guild KJ, et al. 2009. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J. Exp. Med. 206:655-667
208. Xu W, He B, Chiu A, Chadburn A, Shan M, et al. 2007. Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nat. Immunol. 8:294-303
209. Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H, et al. 2004. Impaired IgA class switching in APRIL-deficient mice. Proc. Natl. Acad. Sci. USA 101:3903-3908
210. Castigli E, Wilson S, Garibyan L, Rachid R, Bonilla F, et al. 2007. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat. Genet. 39:430-431
211. Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, et al. 2005. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat. Genet. 37:820-828
212. Chu VT, Enghard P, Riemekasten G, Berek C. 2007. In vitro and in vivo activation induces BAFF and APRIL expression in B cells. J. Immunol. 179:5947-5957
213. McCarthy DD, ChiuS, GaoY, Summers-deLuca LE, Gommerman JL. 2006. BAFF inducesahyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT. Cell. Immunol. 241:85-94
214. Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, et al. 2009. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat. Immunol. 10:778-785
215. Macpherson AJ. 2006. IgA adaptation to the presence of commensal bacteria in the intestine. Curr. Top. Microbiol. Immunol. 308:117-136
216. Burt RW, Jacoby RF. 1999. Polyposis syndromes. In Textbook of Gastroenterology, ed. T Yamada, D Alpers, L Laine, C Owyang, D Powell, pp. 1995-2022. Philadelphia: Lippincott William & Wilkins
217. Harriman GR, Bogue M, Rogers P, Finegold M, Pacheco S, et al. 1999. Targeted deletion of the IgA constant region in mice leads to IgA deficiency with alterations in expression of other Ig isotypes. J. Immunol. 162:2521-2529
218. Lycke N, Erlandsson L, Ekman L, Schon K, 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
219. Johansen FE, Pekna M, Norderhaug IN, Haneberg B, Hietala MA, et al. 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
220. Harris NL, Spoerri I, Schopfer JF, Nembrini C, Merky P, et al. 2006. Mechanisms of neonatal mucosal antibody protection. J. Immunol. 177:6256-6262
221. Macpherson AJ, UhrT. 2004. Inductionofprotective IgA byintestinal dendritic cells carrying commensal bacteria. Science 303:1662-1665
222. Sait LC, Galic M, Price JD, Simpfendorfer KR, Diavatopoulos DA, et al. 2007. Secretory antibodies reduce systemic antibody responses against the gastrointestinal commensal flora. Int. Immunol. 19:257-265
223. Wijburg OL, Uren TK, Simpfendorfer K, Johansen FE, Brandtzaeg P, Strugnell RA. 2006. Innate secretory antibodies protect against natural Salmonella typhimurium infection. J. Exp. Med. 203:21-26
224. Suzuki K, Meek B, Doi Y, Muramatsu M, Chiba T, et al. 2004. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc. Natl. Acad. Sci. USA 101:1981-1986
225. Davis CP, Savage DC. 1974. Habitat, succession, attachment, and morphologyofsegmented, filamentous microbes indigenous to the murine gastrointestinal tract. Infect. Immun. 10:948-956
226. Ohashi Y, Hiraguchi M, Ushida K. 2006. The composition of intestinal bacteria affects the level of luminal IgA. Biosci. Biotechnol. Biochem. 70:3031-3035
227. Durandy A, Taubenheim N, Peron S, Fischer A. 2007. Pathophysiology of B-cell intrinsic immunoglob-ulin class switch recombination deficiencies. Adv. Immunol. 94:275-306
228. Bastlein C, Burlefinger R, Holzberg E, Voeth C, Garbrecht M, Ottenjann R. 1988. Common variable immunodeficiency syndrome and nodular lymphoid hyperplasia in the small intestine. Endoscopy 20:272-275
229. Zaheen A, Boulianne B, Parsa JY, Ramachandran S, Gommerman JL, Martin A. 2009. AID constrains germinal center size by rendering B cells susceptible to apoptosis. Blood 114:547-554
230. Fernandez MI, Pedron T, Tournebize R, Olivo-Marin JC, Sansonetti PJ, Phalipon A. 2003. Anti-inflammatory role for intracellular dimeric immunoglobulin A by neutralization of lipopolysaccharide in epithelial cells. Immunity 18:739-749
231. Peterson DA, McNulty NP, Guruge JL, Gordon JI. 2007. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2:328-339