Skip to main content

Advertisement

SpringerLink
Log in

Regulation of intestinal IgA responses

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

The intestine harbors enormous numbers of commensal bacteria and is under frequent attack from food-borne pathogens and toxins. A properly regulated immune response is critical for homeostatic maintenance of commensals and for protection against infection and toxins in the intestine. Immunoglobulin A (IgA) isotype antibodies function specifically in mucosal sites such as the intestines to help maintain intestinal health by binding to and regulating commensal microbiota, pathogens and toxins. IgA antibodies are produced by intestinal IgA antibody-secreting plasma cells generated in gut-associated lymphoid tissues from naïve B cells in response to stimulations of the intestinal bacteria and components. Research on generation, migration, and maintenance of IgA-secreting cells is important in our effort to understand the biology of IgA responses and to help better design vaccines against intestinal infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

AID:

Activation-induced cytidine deaminase

APRIL:

A proliferation-inducing ligand

BAFF:

B cell activating factor

BCMA:

B cell maturation antigen

BCR:

B cell receptor

CP:

Caecal patch

CSR:

Class switch recombination

CT:

Cholera toxin

DC:

Dendritic cell

GALT:

Gut-associated lymphoid tissue

GF:

Germ-free

IgA:

Immunoglobulin A

IgA-ASC:

IgA antibody-secreting plasma cell

IgH:

Immunoglobulin heavy chain

ILC:

Innate lymphoid cell

ILF:

Isolated lymphoid follicle

LP:

Lamina propria

LTi:

Lymphoid tissue inducer

MLN:

Mesenteric lymph node

PD-1:

Programmed cell death-1

pDC:

Plasmacytoid dendritic cell

pIgR:

Polymeric immunoglobulin receptor

PP:

Peyer’s patch

RA:

Retinoic acid

RAG:

Recombinase-activating gene

SFB:

Segmented filamentous bacteria

SHM:

Somatic hypermutation

SIgA:

Secretory IgA

TCR:

T cell receptor

Tfh:

Follicular T help

Tfr:

Follicular regulatory T

TGF-β1:

Transforming growth factor β1

TH17:

T helper 17

Treg:

Regulatory T

References

  1. Brandtzaeg P, Prydz H (1984) Direct evidence for an integrated function of J chain and secretory component in epithelial transport of immunoglobulins. Nature 311(5981):71–73

    Article  CAS  PubMed  Google Scholar 

  2. Kawamoto S, Maruya M, Kato LM, Suda W, Atarashi K, Doi Y, Tsutsui Y, Qin H, Honda K, Okada T et al (2014) Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41(1):152–165

  3. Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y, Tsutsui Y, Kato LM, Fagarasan S (2012) The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science 336(6080):485–489

  4. Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W et al (2014) Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158(5):1000–1010

    Article  CAS  PubMed  Google Scholar 

  5. Corthesy B (2007) Roundtrip ticket for secretory IgA: role in mucosal homeostasis? J Immunol 178(1):27–32

    Article  CAS  PubMed  Google Scholar 

  6. Cerutti A, Rescigno M (2008) The biology of intestinal immunoglobulin A responses. Immunity 28(6):740–750

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Mantis NJ, Rol N, Corthesy B (2011) Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4(6):603–611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Boullier S, Tanguy M, Kadaoui KA, Caubet C, Sansonetti P, Corthesy B, Phalipon A (2009) Secretory IgA-mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down-regulating inflammatory circuits. J Immunol 183(9):5879–5885

    Article  CAS  PubMed  Google Scholar 

  9. Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, Kaminogawa S, Takahashi-Iwanaga H, Iwanaga T, Kiyono H et al (2002) Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 168(1):57–64

    Article  CAS  PubMed  Google Scholar 

  10. 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 beta receptor, and TNF receptor I function. J Immunol 170(11):5475–5482

    Article  CAS  PubMed  Google Scholar 

  11. Bouskra D, Brezillon C, Berard M, Werts C, Varona R, Boneca IG, Eberl G (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456(7221):507–510

    Article  CAS  PubMed  Google Scholar 

  12. Lorenz RG, Newberry RD (2004) Isolated lymphoid follicles can function as sites for induction of mucosal immune responses. Ann N Y Acad Sci 1029:44–57

    Article  CAS  PubMed  Google Scholar 

  13. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov II, Itoh K, Littman DR, Fagarasan S (2008) Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 29(2):261–271

    Article  CAS  PubMed  Google Scholar 

  14. Masahata K, Umemoto E, Kayama H, Kotani M, Nakamura S, Kurakawa T, Kikuta J, Gotoh K, Motooka D, Sato S et al (2014) Generation of colonic IgA-secreting cells in the caecal patch. Nat Commun 5:3704

    Article  PubMed  Google Scholar 

  15. Suzuki K, Fagarasan S (2009) Diverse regulatory pathways for IgA synthesis in the gut. Mucosal Immunol 2(6):468–471

    Article  CAS  PubMed  Google Scholar 

  16. Lin M, Du L, Brandtzaeg P, Pan-Hammarstrom Q (2014) IgA subclass switch recombination in human mucosal and systemic immune compartments. Mucosal Immunol 7(3):511–520

    Article  CAS  PubMed  Google Scholar 

  17. 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(5474):2222–2226

    Article  CAS  PubMed  Google Scholar 

  18. Kroese FG, Butcher EC, Stall AM, Herzenberg LA (1989) A major peritoneal reservoir of precursors for intestinal IgA plasma cells. Immunol Invest 18(1–4):47–58

    Article  CAS  PubMed  Google Scholar 

  19. Kroese FG, Butcher EC, Stall AM, Lalor PA, Adams S, Herzenberg LA (1989) Many of the IgA producing plasma cells in murine gut are derived from self-replenishing precursors in the peritoneal cavity. Int Immunol 1(1):75–84

    Article  CAS  PubMed  Google Scholar 

  20. Macpherson AJ, Slack E (2007) The functional interactions of commensal bacteria with intestinal secretory IgA. Curr Opin Gastroenterol 23(6):673–678

    Article  CAS  PubMed  Google Scholar 

  21. Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian UH (2003) Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 424(6944):88–93

    Article  CAS  PubMed  Google Scholar 

  22. Mora JR, von Andrian UH (2008) Differentiation and homing of IgA-secreting cells. Mucosal Immunol 1(2):96–109

    Article  CAS  PubMed  Google Scholar 

  23. Hapfelmeier S, Lawson MA, Slack E, Kirundi JK, Stoel M, Heikenwalder M, Cahenzli J, Velykoredko Y, Balmer ML, Endt K et al (2010) Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328(5986):1705–1709

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Mesin L, Di Niro R, Thompson KM, Lundin KE, Sollid LM (2011) Long-lived plasma cells from human small intestine biopsies secrete immunoglobulins for many weeks in vitro. J Immunol 187(6):2867–2874

    Article  CAS  PubMed  Google Scholar 

  25. Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, 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(3):264–270

  26. Tangye SG, Ma CS, Brink R, Deenick EK (2013) The good, the bad and the ugly—TFH cells in human health and disease. Nat Rev Immunol 13(6):412–426

    Article  CAS  PubMed  Google Scholar 

  27. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139(3):485–498

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Sczesnak A, Segata N, Qin X, Gevers D, Petrosino JF, Huttenhower C, Littman DR, Ivanov II (2011) The genome of th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment. Cell Host Microbe 10(3):260–272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J, Steinmetz OM, Stockinger B (2013) Plasticity of Th17 cells in Peyer’s patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14(4):372–379

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Cao AT, Yao S, Gong B, Elson CO, Cong Y (2012) Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. J Immunol 189(9):4666–4673

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, Hori S, Fagarasan S (2009) Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer’s patches. Science 323(5920):1488–1492

    Article  CAS  PubMed  Google Scholar 

  32. Cong Y, Feng T, Fujihashi K, Schoeb TR, Elson CO (2009) A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc Natl Acad Sci USA 106(46):19256–19261

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, Srivastava M, Divekar DP, Beaton L, Hogan JJ et al (2011) Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med 17(8):975–982

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S, Wang YH, Lim H, Reynolds JM, Zhou XH et al (2011) Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med 17(8):983–988

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Good-Jacobson KL, Szumilas CG, Chen L, Sharpe AH, Tomayko MM, Shlomchik MJ (2010) PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 11(6):535–542

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Dullaers M, Li D, Xue Y, Ni L, Gayet I, Morita R, Ueno H, Palucka KA, Banchereau J, Oh S (2009) A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. Immunity 30(1):120–129

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Seo GY, Youn J, Kim PH (2009) IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer’s patches. J Leukoc Biol 85(5):744–750

    Article  CAS  PubMed  Google Scholar 

  38. Tezuka H, Abe Y, Asano J, Sato T, Liu J, Iwata M, Ohteki T (2011) Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction. Immunity 34(2):247–257

    Article  CAS  PubMed  Google Scholar 

  39. Hu S, Yang K, Yang J, Li M, Xiong N (2011) Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines. Proc Natl Acad Sci USA 108(45):E1035–E1044

    Article  PubMed Central  PubMed  Google Scholar 

  40. 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(6):1414–1425

    Article  CAS  PubMed  Google Scholar 

  41. Lugering A, Ross M, Sieker M, Heidemann J, Williams IR, Domschke W, Kucharzik T (2010) CCR6 identifies lymphoid tissue inducer cells within cryptopatches. Clin Exp Immunol 160(3):440–449

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Nochi T, Denton PW, Wahl A, Garcia JV (2013) Cryptopatches are essential for the development of human GALT. Cell Rep 3(6):1874–1884

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463(7280):540–544

    Article  CAS  PubMed  Google Scholar 

  44. Kruglov AA, Grivennikov SI, Kuprash DV, Winsauer C, Prepens S, Seleznik GM, Eberl G, Littman DR, Heikenwalder M, Tumanov AV et al (2013) Nonredundant function of soluble LTalpha3 produced by innate lymphoid cells in intestinal homeostasis. Science 342(6163):1243–1246

    Article  CAS  PubMed  Google Scholar 

  45. Kunkel EJ, Kim CH, Lazarus NH, Vierra MA, Soler D, Bowman EP, Butcher EC (2003) CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells. J Clin Investig 111(7):1001–1010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Bowman EP, Kuklin NA, Youngman KR, Lazarus NH, Kunkel EJ, Pan J, Greenberg HB, Butcher EC (2002) The intestinal chemokine thymus-expressed chemokine (CCL25) attracts IgA antibody-secreting cells. J Exp Med 195(2):269–275

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Pabst O, Ohl L, Wendland M, Wurbel MA, Kremmer E, Malissen B, Forster R (2004) Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine. J Exp Med 199(3):411–416

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Gohda M, Kunisawa J, Miura F, Kagiyama Y, Kurashima Y, Higuchi M, Ishikawa I, Ogahara I, Kiyono H (2008) Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer’s patches for intestinal IgA responses. J Immunol 180(8):5335–5343

    Article  CAS  PubMed  Google Scholar 

  49. Hieshima K, Kawasaki Y, Hanamoto H, Nakayama T, Nagakubo D, Kanamaru A, Yoshie O (2004) CC chemokine ligands 25 and 28 play essential roles in intestinal extravasation of IgA antibody-secreting cells. J Immunol 173(6):3668–3675

    Article  CAS  PubMed  Google Scholar 

  50. Lazarus NH, Kunkel EJ, Johnston B, Wilson E, Youngman KR, Butcher EC (2003) A common mucosal chemokine (mucosae-associated epithelial chemokine/CCL28) selectively attracts IgA plasmablasts. J Immunol 170(7):3799–3805

    Article  CAS  PubMed  Google Scholar 

  51. Mei HE, Yoshida T, Sime W, Hiepe F, Thiele K, Manz RA, Radbruch A, Dorner T (2009) Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood 113(11):2461–2469

    Article  CAS  PubMed  Google Scholar 

  52. Pan J, Kunkel EJ, Gosslar U, Lazarus N, Langdon P, Broadwell K, Vierra MA, Genovese MC, Butcher EC, Soler D (2000) A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues. J Immunol 165(6):2943–2949

    Article  CAS  PubMed  Google Scholar 

  53. Wang W, Soto H, Oldham ER, Buchanan ME, Homey B, Catron D, Jenkins N, Copeland NG, Gilbert DJ, Nguyen N et al (2000) Identification of a novel chemokine (CCL28), which binds CCR10 (GPR2). J Biol Chem 275(29):22313–22323

    Article  CAS  PubMed  Google Scholar 

  54. Feng N, Jaimes MC, Lazarus NH, Monak D, Zhang C, Butcher EC, Greenberg HB (2006) Redundant role of chemokines CCL25/TECK and CCL28/MEC in IgA+ plasmablast recruitment to the intestinal lamina propria after rotavirus infection. J Immunol 176(10):5749–5759

    Article  CAS  PubMed  Google Scholar 

  55. Morteau O, Gerard C, Lu B, Ghiran S, Rits M, Fujiwara Y, Law Y, Distelhorst K, Nielsen EM, Hill ED et al (2008) An indispensable role for the chemokine receptor CCR10 in IgA antibody-secreting cell accumulation. J Immunol 181(9):6309–6315

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Jin Y, Xia M, Sun A, Saylor CM, Xiong N (2010) CCR10 Is important for the development of skin-specific {gamma}{delta}T cells by regulating their migration and location. J Immunol 185(10):5723–5731

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Wagner N, Lohler J, Kunkel EJ, Ley K, Leung E, Krissansen G, Rajewsky K, Muller W (1996) Critical role for beta7 integrins in formation of the gut-associated lymphoid tissue. Nature 382(6589):366–370

    Article  CAS  PubMed  Google Scholar 

  58. Mora JR, Iwata M, Eksteen B, Song SY, Junt T, Senman B, Otipoby KL, Yokota A, Takeuchi H, Ricciardi-Castagnoli P et al (2006) Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314(5802):1157–1160

    Article  CAS  PubMed  Google Scholar 

  59. Hammerschmidt SI, Friedrichsen M, Boelter J, Lyszkiewicz M, Kremmer E, Pabst O, Forster R (2011) Retinoic acid induces homing of protective T and B cells to the gut after subcutaneous immunization in mice. J Clin Invest 121(8):3051–3061

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Hammerschmidt SI, Ahrendt M, Bode U, Wahl B, Kremmer E, Forster R, Pabst O (2008) Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. J Exp Med 205(11):2483–2490

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Molenaar R, Greuter M, van der Marel AP, Roozendaal R, Martin SF, Edele F, Huehn J, Forster R, O’Toole T, Jansen W et al (2009) Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J Immunol 183(10):6395–6402

    Article  CAS  PubMed  Google Scholar 

  62. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY (2004) Retinoic acid imprints gut-homing specificity on T cells. Immunity 21(4):527–538

    Article  CAS  PubMed  Google Scholar 

  63. Shirakawa AK, Nagakubo D, Hieshima K, Nakayama T, Jin Z, Yoshie O (2008) 1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells. J Immunol 180(5):2786–2795

    Article  CAS  PubMed  Google Scholar 

  64. Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC (2007) DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol 8(3):285–293

    Article  CAS  PubMed  Google Scholar 

  65. Yanagibashi T, Hosono A, Oyama A, Tsuda M, Suzuki A, Hachimura S, Takahashi Y, Momose Y, Itoh K, Hirayama K et al (2013) IgA production in the large intestine is modulated by a different mechanism than in the small intestine: bacteroides acidifaciens promotes IgA production in the large intestine by inducing germinal center formation and increasing the number of IgA+ B cells. Immunobiology 218(4):645–651

    Article  CAS  PubMed  Google Scholar 

  66. Lecuyer E, Rakotobe S, Lengline-Garnier H, Lebreton C, Picard M, Juste C, Fritzen R, Eberl G, McCoy KD, Macpherson AJ et al (2014) Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity 40(4):608–620

    Article  CAS  PubMed  Google Scholar 

  67. Agnello D, Denimal D, Lavaux A, Blondeau-Germe L, Lu B, Gerard NP, Gerard C, Pothier P (2013) Intrarectal immunization and IgA antibody-secreting cell homing to the small intestine. J Immunol 190(9):4836–4847

    CAS  PubMed  Google Scholar 

  68. Cerutti A (2011) Immunology. IgA changes the rules of memory. Science 328(5986):1646–1647

    Article  Google Scholar 

  69. Yuvaraj S, Dijkstra G, Burgerhof JG, Dammers PM, Stoel M, Visser A, Kroese FG, Bos NA (2009) Evidence for local expansion of IgA plasma cell precursors in human ileum. J Immunol 183(8):4871–4878

    Article  CAS  PubMed  Google Scholar 

  70. Lindner C, Wahl B, Fohse L, Suerbaum S, Macpherson AJ, Prinz I, Pabst O (2012) Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. J Exp Med 209(2):365–377

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Lycke N, Holmgren J (1987) Long-term cholera antitoxin memory in the gut can be triggered to antibody formation associated with protection within hours of an oral challenge immunization. Scand J Immunol 25(4):407–412

    Article  CAS  PubMed  Google Scholar 

  72. Lycke N, Holmgren J (1989) Adoptive transfer of gut mucosal antitoxin memory by isolated B cells 1 year after oral immunization with cholera toxin. Infect Immun 57(4):1137–1141

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Vajdy M, Lycke N (1993) Stimulation of antigen-specific T- and B-cell memory in local as well as systemic lymphoid tissues following oral immunization with cholera toxin adjuvant. Immunology 80(2):197–203

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Williams MB, Rose JR, Rott LS, Franco MA, Greenberg HB, Butcher EC (1998) The memory B cell subset responsible for the secretory IgA response and protective humoral immunity to rotavirus expresses the intestinal homing receptor, alpha4beta7. J Immunol 161(8):4227–4235

    CAS  PubMed  Google Scholar 

  75. Tengvall S, Lundgren A, Quiding-Jarbrink M, Svennerholm AM (2010) BAFF, stimulatory DNA and IL-15 stimulates IgA(+) memory B cells and provides a novel approach for analysis of memory responses to mucosal vaccines. Vaccine 28(33):5445–5450

    Article  CAS  PubMed  Google Scholar 

  76. Bemark M, Boysen P, Lycke NY (2012) Induction of gut IgA production through T cell-dependent and T cell-independent pathways. Ann N Y Acad Sci 1247:97–116

    Article  CAS  PubMed  Google Scholar 

  77. Huard B, McKee T, Bosshard C, Durual S, Matthes T, Myit S, Donze O, Frossard C, Chizzolini C, Favre C et al (2008) APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa. J Clin Invest 118(8):2887–2895

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Cassese G, Arce S, Hauser AE, Lehnert K, Moewes B, Mostarac M, Muehlinghaus G, Szyska M, Radbruch A, Manz RA (2003) Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J Immunol 171(4):1684–1690

    Article  CAS  PubMed  Google Scholar 

  79. Chu VT, Beller A, Nguyen TT, Steinhauser G, Berek C (2011) The long-term survival of plasma cells. Scand J Immunol 73(6):508–511

    Article  CAS  PubMed  Google Scholar 

  80. Pinto D, Montani E, Bolli M, Garavaglia G, Sallusto F, Lanzavecchia A, Jarrossay D (2013) A functional BCR in human IgA and IgM plasma cells. Blood 121(20):4110–4114

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was partly supported by a grant from National Institute of Health (NIH) and institutional funds of the Pennsylvania State University (to Na Xiong). We thank Micha Davila for editorial help.

Author information

Authors and Affiliations

  1. Department of Veterinary and Biomedical Sciences, Centre for Molecular Immunology and Infectious Disease, The Pennsylvania State University, 115 Henning Building, University Park, PA, 16802, USA

    Na Xiong & Shaomin Hu

Authors
  1. Na Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaomin Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Na Xiong.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiong, N., Hu, S. Regulation of intestinal IgA responses. Cell. Mol. Life Sci. 72, 2645–2655 (2015). https://doi.org/10.1007/s00018-015-1892-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-015-1892-4

Keywords

Search

Navigation