1932

Abstract

IgA is the dominant immunoglobulin isotype produced in mammals, largely secreted across the intestinal mucosal surface. Although induction of IgA has been a hallmark feature of microbiota colonization following colonization in germ-free animals, until recently appreciation of the function of IgA in host-microbial mutualism has depended mainly on indirect evidence of alterations in microbiota composition or penetration of microbes in the absence of somatic mutations in IgA (or compensatory IgM). Highly parallel sequencing techniques that enable high-resolution analysis of either microbial consortia or IgA sequence diversity are now giving us new perspectives on selective targeting of microbial taxa and the trajectory of IgA diversification according to induction mechanisms, between different individuals and over time. The prospects are to link the range of diversified IgA clonotypes to specific antigenic functions in modulating the microbiota composition, position and metabolism to ensure host mutualism.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-042617-053238
2018-04-26
2024-06-18
Loading full text...

Full text loading...

/deliver/fulltext/immunol/36/1/annurev-immunol-042617-053238.html?itemId=/content/journals/10.1146/annurev-immunol-042617-053238&mimeType=html&fmt=ahah

Literature Cited

  1. Kaetzel CS, Robinson JK, Lamm ME. 1.  1994. Epithelial transcytosis of monomeric IgA and IgG cross-linked through antigen to polymeric IgA: a role for monomeric antibodies in the mucosal immune system. J. Immunol. 152:72–6 [Google Scholar]
  2. Kadaoui KA, Corthesy B. 2.  2007. Secretory IgA mediates bacterial translocation to dendritic cells in mouse Peyer's patches with restriction to mucosal compartment. J. Immunol. 179:7751–57 [Google Scholar]
  3. Macpherson AJ, Uhr T. 3.  2004. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303:1662–65 [Google Scholar]
  4. Lycke N, Eriksen L, Holmgren J. 4.  1987. Protection against cholera toxin after oral immunisation is thymus dependent and associated with intestinal production of neutralising IgA antitoxin. Scand. J. Immunol. 25:413–19 [Google Scholar]
  5. Kaetzel CS, Robinson JK, Chintalacharuvu KR, Vaerman JP, Lamm ME. 5.  1991. The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. PNAS 88:8796–800 [Google Scholar]
  6. Burns JW, Siadat-Pajouh M, Krishnaney AA, Greenberg HB. 6.  1996. Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity. Science 272:104–7 [Google Scholar]
  7. Peterson DA, McNulty NP, Guruge JL, Gordon JI. 7.  2007. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2:328–39 [Google Scholar]
  8. Kramer DR, Cebra JJ. 8.  1995. Early appearance of “natural” mucosal IgA responses and germinal centers in suckling mice developing in the absence of maternal antibodies. J. Immunol. 154:2051–62 [Google Scholar]
  9. Harris NL, Spoerri I, Schopfer JF, Nembrini C, Merky P. 9.  et al. 2006. Mechanisms of neonatal mucosal antibody protection. J. Immunol. 177:6256–62 [Google Scholar]
  10. Rogier EW, Frantz AL, Bruno ME, Wedlund L, Cohen DA. 10.  et al. 2014. Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. PNAS 111:3074–79 [Google Scholar]
  11. Bachmann MF, Zinkernagel RM. 11.  1997. Neutralizing antiviral B cell responses. Annu. Rev. Immunol. 15:235–70 [Google Scholar]
  12. Holmes E, Li JV, Athanasiou T, Ashrafian H, Nicholson JK. 12.  2011. Understanding the role of gut microbiome-host metabolic signal disruption in health and disease. Trends Microbiol 19:349–59 [Google Scholar]
  13. Pierce NF, Gowans JL. 13.  1975. Cellular kinetics of the intestinal immune response to cholera toxoid in rats. J. Exp. Med. 142:1550–63 [Google Scholar]
  14. Elson CO, Ealding W. 14.  1984. Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. J. Immunol. 133:2892–97 [Google Scholar]
  15. Lycke N, Holmgren J. 15.  1986. Intestinal mucosal memory and presence of memory cells in lamina propria and Peyer's patches in mice 2 years after oral immunization with cholera toxin. Scand. J. Immunol. 23:611–16 [Google Scholar]
  16. Macpherson AJ, Hunziker L, McCoy K, Lamarre A. 16.  2001. IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect 3:1021–35 [Google Scholar]
  17. Macpherson AJ, McCoy KD. 17.  2015. Standardised animal models of host microbial mutualism. Mucosal Immunol 8:476–86 [Google Scholar]
  18. Fagarasan S, Kawamoto S, Kanagawa O, Suzuki K. 18.  2010. Adaptive immune regulation in the gut: T cell–dependent and T cell–independent IgA synthesis. Annu. Rev. Immunol. 28:243–73 [Google Scholar]
  19. Cerutti A, Chen K, Chorny A. 19.  2011. Immunoglobulin responses at the mucosal interface. Annu. Rev. Immunol. 29:273–93 [Google Scholar]
  20. Fagarasan S, Macpherson AJ. 20.  2015. The regulation of IgA production. Mucosal Immunology J Mestecky, W Strobel, MW Russell, BL Kelsall, H Cheroutre, BN Lambrecht 471–85 Oxford, UK: Elsevier [Google Scholar]
  21. Reboldi A, Cyster JG. 21.  2016. Peyer's patches: organizing B-cell responses at the intestinal frontier. Immunol. Rev. 271:230–45 [Google Scholar]
  22. Jorgensen GH, Gardulf A, Sigurdsson MI, Sigurdardottir ST, Thorsteinsdottir I. 22.  et al. 2013. Clinical symptoms in adults with selective IgA deficiency: a case-control study. J. Clin. Immunol. 33:742–47 [Google Scholar]
  23. Singh K, Chang C, Gershwin ME. 23.  2014. IgA deficiency and autoimmunity. Autoimmun. Rev. 13:163–77 [Google Scholar]
  24. Takahashi N, Kondo T, Fukuta M, Takemoto A, Takami Y. 24.  et al. 2013. Selective IgA deficiency mimicking Churg-Strauss syndrome and hypereosinophilic syndrome: a case report. Nagoya J. Med. Sci 75:139–46 [Google Scholar]
  25. Iervolino S, Lofrano M, Di Minno MN, Foglia F, Scarpa R, Peluso R. 25.  2012. Clinical manifestation of selective IgA deficiency evidence after anti-TNF-α treatment in a psoriatic arthritis patient: case report. Reumatismo 64:40–43 [Google Scholar]
  26. Jorgensen SF, Reims HM, Frydenlund D, Holm K, Paulsen V. 26.  et al. 2016. A cross-sectional study of the prevalence of gastrointestinal symptoms and pathology in patients with common variable immunodeficiency. Am. J. Gastroenterol. 111:1467–75 [Google Scholar]
  27. Brandtzaeg P, Prydz H. 27.  1984. Direct evidence for an integrated function of J chain and secretory component in epithelial transport of immunoglobulins. Nature 311:71–73 [Google Scholar]
  28. Mbawuike IN, Pacheco S, Acuna CL, Switzer KC, Zhang Y, Harriman GR. 28.  1999. Mucosal immunity to influenza without IgA: an IgA knockout mouse model. J. Immunol. 162:2530–37 [Google Scholar]
  29. Harriman GR, Bogue M, Rogers P, Finegold M, Pacheco S. 29.  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. 162:2521–29 [Google Scholar]
  30. Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T. 30.  2002. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298:1424–27 [Google Scholar]
  31. Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T. 31.  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. 12:264–70 [Google Scholar]
  32. Johansen FE, Pekna M, Norderhaug IN, Haneberg B, Hietala MA. 32.  et al. 1999. Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice. J. Exp. Med. 190:915–22 [Google Scholar]
  33. Reikvam DH, Derrien M, Islam R, Erofeev A, Grcic V. 33.  et al. 2012. Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice. Eur. J. Immunol. 42:2959–70 [Google Scholar]
  34. Reikvam DH, Erofeev A, Sandvik A, Grcic V, Jahnsen FL. 34.  et al. 2011. Depletion of murine intestinal microbiota: effects on gut mucosa and epithelial gene expression. PLOS ONE 6:e17996 [Google Scholar]
  35. Rigoni R, Fontana E, Guglielmetti S, Fosso B, D'Erchia AM. 35.  et al. 2016. Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects. J. Exp. Med. 213:355–75 [Google Scholar]
  36. Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J. 36.  et al. 2014. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158:1000–10 [Google Scholar]
  37. Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T. 37.  et al. 2015. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci. Transl. Med. 7:276ra24 [Google Scholar]
  38. Bunker JJ, Flynn TM, Koval JC, Shaw DG, Meisel M. 38.  et al. 2015. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A. Immunity 43:541–53 [Google Scholar]
  39. Planer JD, Peng Y, Kau AL, Blanton LV, Ndao IM. 39.  et al. 2016. Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. Nature 534:263–66 [Google Scholar]
  40. Moon C, Baldridge MT, Wallace MA, Burnham CA, Virgin HW, Stappenbeck TS. 40.  2015. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature 521:90–93 [Google Scholar]
  41. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. 41.  2008. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. PNAS 105:15064–69 [Google Scholar]
  42. Sczesnak A, Segata N, Qin X, Gevers D, Petrosino JF. 42.  et al. 2011. The genome of Th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment. Cell Host Microbe 10:260–72 [Google Scholar]
  43. Klaasen HL, Van der Heijden PJ, Stok W, Poelma FG, Koopman JP. 43.  et al. 1993. Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice. Infect. Immun. 61:303–6 [Google Scholar]
  44. Jiang HQ, Bos NA, Cebra JJ. 44.  2001. Timing, localization, and persistence of colonization by segmented filamentous bacteria in the neonatal mouse gut depend on immune status of mothers and pups. Infect. Immun. 69:3611–17 [Google Scholar]
  45. Kawamoto S, Maruya M, Kato LM, Suda W, Atarashi K. 45.  et al. 2014. Foxp3+ T cells regulate immunoglobulin A selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41:152–65 [Google Scholar]
  46. Viladomiu M, Kivolowitz C, Abdulhamid A, Dogan B, Victorio D. 46.  et al. 2017. IgA-coated E. coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation. Sci. Transl. Med. 9:eaaf9655 [Google Scholar]
  47. Vos T, Lopez AD, Murray CJL. 47. ; for GBD 2013 Mortality and Causes of Death Collaborators. 2015. Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385:117–71 [Google Scholar]
  48. Grantham-McGregor S, Cheung YB, Cueto S, Glewwe P, Richter L, Strupp B. 48. ; for Int. Child Dev. Steer. Group. 2007. Developmental potential in the first 5 years for children in developing countries. Lancet 369:60–70 [Google Scholar]
  49. Walker SP, Wachs TD, Gardner JM, Lozoff B, Wasserman GA. 49.  et al.; for Int. Child Dev. Steer. Group. 2007. Child development: risk factors for adverse outcomes in developing countries. Lancet 369:145–57 [Google Scholar]
  50. Korpe PS, Petri WA Jr.. 50.  2012. Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol. Med. 18:328–36 [Google Scholar]
  51. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R. 51.  et al. 2013. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339:548–54 [Google Scholar]
  52. Blanton LV, Barratt MJ, Charbonneau MR, Ahmed T, Gordon JI. 52.  2016. Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics. Science 352:1533 [Google Scholar]
  53. Trehan I, Goldbach HS, LaGrone LN, Meuli GJ, Wang RJ. 53.  et al. 2013. Antibiotics as part of the management of severe acute malnutrition. N. Engl. J. Med 368:425–35 [Google Scholar]
  54. Beatty DW, Napier B, Sinclair-Smith CC, McCabe K, Hughes EJ. 54.  1983. Secretory IgA synthesis in kwashiorkor. J. Clin. Lab. Immunol 12:31–6 [Google Scholar]
  55. Connolly J. 55.  2006. The Book of Lost Things New York: Wash. Sq. [Google Scholar]
  56. Chodirker WB, Tomasi TB. 56.  1963. Gamma globulins: quantitative relationships in human serum and non-vascular fluids. Science 142:1080–81 [Google Scholar]
  57. Weisz-Carrington P, Roux ME, Lamm ME. 57.  1977. Plasma cells and epithelial immunoglobulins in the mouse mammary gland during pregnancy and lactation. J. Immunol. 119:1306–7 [Google Scholar]
  58. Koch MA, Reiner GL, Lugo KA, Kreuk LS, Stanbery AG. 58.  et al. 2016. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. Cell 165:827–41 [Google Scholar]
  59. Roux ME, McWilliams M, Phillips-Quagliata JM, Weisz-Carrington P, Lamm ME. 59.  1977. Origin of IgA-secreting plasma cells in the mammary gland. J. Exp. Med. 146:1311–22 [Google Scholar]
  60. Halsey JF, Mitchell C, Meyer R, Cebra JJ. 60.  1982. Metabolism of immunoglobulin A in lactating mice: origins of immunoglobulin A in milk. Eur. J. Immunol. 12:107–12 [Google Scholar]
  61. Vorbach C, Capecchi MR, Penninger JM. 61.  2006. Evolution of the mammary gland from the innate immune system?. BioEssays 28:606–16 [Google Scholar]
  62. Ghetie V, Ward ES. 62.  1997. FcRn: the MHC class I-related receptor that is more than an IgG transporter. Immunol. Today 18:592–98 [Google Scholar]
  63. Jacobowitz Israel E, Patel VK, Taylor SF, Marshak-Rothstein A, Simister NE. 63.  1995. Requirement for a beta 2-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice. J. Immunol. 154:6246–51 [Google Scholar]
  64. Oda H, Wakabayashi H, Yamauchi K, Abe F. 64.  2014. Lactoferrin and bifidobacteria. Biometals 27:915–22 [Google Scholar]
  65. Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. 65.  2007. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Hum. Dev. 83:335–39 [Google Scholar]
  66. Charbonneau MR, O'Donnell D, Blanton LV, Totten SM, Davis JC. 66.  et al. 2016. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell 164:859–71 [Google Scholar]
  67. Weiss GA, Chassard C, Hennet T. 67.  2014. Selective proliferation of intestinal Barnesiella under fucosyllactose supplementation in mice. Br. J. Nutr. 111:1602–10 [Google Scholar]
  68. Mata LJ, Urrutia JJ, Garcia B, Fernandez R, Behar M. 68.  1969. Shigella infection in breast-fed Guatemalan Indian neonates. Am. J. Dis. Child 117:142–46 [Google Scholar]
  69. Ohashi Y, Hiraguchi M, Sunaba C, Tanaka C, Fujisawa T, Ushida K. 69.  2010. Colonization of segmented filamentous bacteria and its interaction with the luminal IgA level in conventional mice. Anaerobe 16:543–46 [Google Scholar]
  70. Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y. 70.  et al. 2016. The maternal microbiota drives early postnatal innate immune development. Science 351:1296–302 [Google Scholar]
  71. Craig SW, Cebra JJ. 71.  1971. Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J. Exp. Med. 134:188–200 [Google Scholar]
  72. Suzuki K, Maruya M, Kawamoto S, Sitnik K, Kitamura H. 72.  et al. 2010. The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut. Immunity 33:71–83 [Google Scholar]
  73. Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D, Cyster JG. 73.  2016. IgA production requires B cell interaction with subepithelial dendritic cells in Peyer's patches. Science 352:aaf4822 [Google Scholar]
  74. Bergqvist P, Gardby E, Stensson A, Bemark M, Lycke NY. 74.  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. 177:7772–83 [Google Scholar]
  75. Bergqvist P, Stensson A, Lycke NY, Bemark M. 75.  2010. T cell-independent IgA class switch recombination is restricted to the GALT and occurs prior to manifest germinal center formation. J. Immunol. 184:3545–53 [Google Scholar]
  76. He B, Santamaria R, Xu W, Cols M, Chen K. 76.  et al. 2010. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat. Immunol. 11:836–45 [Google Scholar]
  77. Gutzeit C, Magri G, Cerutti A. 77.  2014. Intestinal IgA production and its role in host-microbe interaction. Immunol. Rev. 260:76–85 [Google Scholar]
  78. Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H. 78.  et al. 2004. Impaired IgA class switching in APRIL-deficient mice. PNAS 101:3903–8 [Google Scholar]
  79. Castigli E, Wilson SA, Scott S, Dedeoglu F, Xu S. 79.  et al. 2005. TACI and BAFF-R mediate isotype switching in B cells. J. Exp. Med. 201:35–39 [Google Scholar]
  80. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K. 80.  et al. 2008. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 29:261–71 [Google Scholar]
  81. Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM. 81.  2000. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288:2222–26 [Google Scholar]
  82. Owens WE, Berg RD. 82.  1980. Bacterial translocation from the gastrointestinal tract of athymic (nu/nu) mice. Infect. Immun. 27:461–67 [Google Scholar]
  83. Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y. 83.  et al. 2012. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science 336:485–89 [Google Scholar]
  84. Hapfelmeier S, Lawson MA, Slack E, Kirundi JK, Stoel M. 84.  et al. 2010. Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328:1705–9 [Google Scholar]
  85. Lindner C, Thomsen I, Wahl B, Ugur M, Sethi MK. 85.  et al. 2015. Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Nat. Immunol. 16:880–88 [Google Scholar]
  86. Bemark M, Hazanov H, Stromberg A, Komban R, Holmqvist J. 86.  et al. 2016. Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization. Nat. Commun. 7:12698 [Google Scholar]
  87. Casola S, Otipoby KL, Alimzhanov M, Humme S, Uyttersprot N. 87.  et al. 2004. B cell receptor signal strength determines B cell fate. Nat. Immunol. 5:317–27 [Google Scholar]
  88. Yeap LS, Hwang JK, Du Z, Meyers RM, Meng FL. 88.  et al. 2015. Sequence-intrinsic mechanisms that target AID mutational outcomes on antibody genes. Cell 163:1124–37 [Google Scholar]
  89. Bergqvist P, Stensson A, Hazanov L, Holmberg A, Mattsson J. 89.  et al. 2013. Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses. Mucosal Immunol 6:122–35 [Google Scholar]
  90. Lycke NY, Bemark M. 90.  2012. The role of Peyer's patches in synchronizing gut IgA responses. Front. Immunol. 3:329 [Google Scholar]
  91. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T. 91.  et al. 2011. Enterotypes of the human gut microbiome. Nature 473:174–80 [Google Scholar]
  92. 92. Hum. Microbiome Proj. Consort. 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–14 [Google Scholar]
  93. Schloissnig S, Arumugam M, Sunagawa S, Mitreva M, Tap J. 93.  et al. 2013. Genomic variation landscape of the human gut microbiome. Nature 493:45–50 [Google Scholar]
  94. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T. 94.  et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–98 [Google Scholar]
  95. Yang Y, Torchinsky MB, Gobert M, Xiong H, Xu M. 95.  et al. 2014. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510:152–56 [Google Scholar]
  96. Lecuyer E, Rakotobe S, Lengline-Garnier H, Lebreton C, Picard M. 96.  et al. 2014. Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity 40:608–20 [Google Scholar]
  97. Gagliani N, Amezcua Vesely MC, Iseppon A, Brockmann L, Xu H. 97.  et al. 2015. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 523:221–25 [Google Scholar]
  98. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S. 98.  et al. 2011. Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 17:975–82 [Google Scholar]
  99. Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J. 99.  et al. 2013. Plasticity of TH17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat. Immunol. 14:372–79 [Google Scholar]
  100. McLoughlin K, Schluter J, Rakoff-Nahoum S, Smith AL, Foster KR. 100.  2016. Host selection of microbiota via differential adhesion. Cell Host Microbe 19:550–59 [Google Scholar]
  101. Hunziker L, Recher M, Macpherson AJ, Ciurea A, Freigang S. 101.  et al. 2003. Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections. Nat. Immunol. 4:343–49 [Google Scholar]
  102. Bachmann MF, Kalinke U, Althage A, Freer G, Burkhart C. 102.  et al. 1997. The role of antibody concentration and avidity in antiviral protection. Science 276:2024–27 [Google Scholar]
  103. Kalinke U, Bucher EM, Ernst B, Oxenius A, Roost HP. 103.  et al. 1996. The role of somatic mutation in the generation of the protective humoral immune response against vesicular stomatitis virus. Immunity 5:639–52 [Google Scholar]
  104. Peterson DA, Planer JD, Guruge JL, Xue L, Downey-Virgin W. 104.  et al. 2015. Characterizing the interactions between a naturally-primed immunoglobulin A and its conserved Bacteroides thetaiotaomicron species-specific epitope in gnotobiotic mice. J. Biol. Chem. 290:12630–49 [Google Scholar]
  105. Fransen F, Zagato E, Mazzini E, Fosso B, Manzari C. 105.  et al. 2015. BALB/c and C57BL/6 mice differ in polyreactive IgA abundance, which impacts the generation of antigen-specific IgA and microbiota diversity. Immunity 43:527–40 [Google Scholar]
  106. Benckert J, Schmolka N, Kreschel C, Zoller MJ, Sturm A. 106.  et al. 2011. The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific. J. Clin. Investig. 121:1946–55 [Google Scholar]
  107. Bunker JJ, Erickson SA, Flynn TM, Henry C, Koval JC. 107.  et al. 2017. Natural polyreactive IgA antibodies coat the intestinal microbiota. Science 358:eaan6619 [Google Scholar]
  108. Kuppers R, Zhao M, Hansmann ML, Rajewsky K. 108.  1993. Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J 12:4955–67 [Google Scholar]
  109. Milstein C. 109.  2004. From the structure of antibodies to the diversification of the immune response. Biosci. Rep. 24:280–301 [Google Scholar]
  110. Georgiou G, Ippolito GC, Beausang J, Busse CE, Wardemann H, Quake SR. 110.  2014. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat. Biotechnol. 32:158–68 [Google Scholar]
  111. Friedensohn S, Khan TA, Reddy ST. 111.  2017. Advanced methodologies in high-throughput sequencing of immune repertoires. Trends Biotechnol 35:203–14 [Google Scholar]
  112. Corcoran MM, Phad GE, Vazquez Bernat N, Stahl-Hennig C, Sumida N. 112.  et al. 2016. Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity. Nat. Commun. 7:13642 [Google Scholar]
  113. Watson CT, Glanville J, Marasco WA. 113.  2017. The individual and population genetics of antibody immunity. Trends Immunol 38:459–70 [Google Scholar]
  114. Lindner C, Wahl B, Fohse L, Suerbaum S, Macpherson AJ. 114.  et al. 2012. Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. J. Exp. Med. 209:365–77 [Google Scholar]
  115. Marx V. 115.  2017. How to deduplicate PCR. Nat. Methods 14:473–76 [Google Scholar]
  116. Collins AM, Wang Y, Roskin KM, Marquis CP, Jackson KJ. 116.  2015. The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370:20140236 [Google Scholar]
  117. Greiff V, Menzel U, Miho E, Weber C, Riedel R. 117.  et al. 2017. Systems analysis reveals high genetic and antigen-driven predetermination of antibody repertoires throughout B cell development. Cell Rep 19:1467–78 [Google Scholar]
  118. Ralph DK, Matsen FA 4th. 118.  2016. Likelihood-based inference of B cell clonal families. PLOS Comput. Biol. 12:e1005086 [Google Scholar]
  119. Murugan A, Mora T, Walczak AM, Callan CG Jr.. 119.  2012. Statistical inference of the generation probability of T-cell receptors from sequence repertoires. PNAS 109:16161–66 [Google Scholar]
  120. Mora T, Walczak AM, Bialek W, Callan CG Jr.. 120.  2010. Maximum entropy models for antibody diversity. PNAS 107:5405–10 [Google Scholar]
  121. Bashford-Rogers RJ, Palser AL, Huntly BJ, Rance R, Vassiliou GS. 121.  et al. 2013. Network properties derived from deep sequencing of human B-cell receptor repertoires delineate B-cell populations. Genome Res 23:1874–84 [Google Scholar]
  122. Miho E, Greiff V, Roskar R, Reddy ST. 122.  2017. The fundamental principles of antibody repertoire architecture revealed by large-scale network analysis. bioRxiv 124578. https://dx.doi.org/10.1101/124578 [Crossref]
  123. Emerson RO, DeWitt WS, Vignali M, Gravley J, Hu JK. 123.  et al. 2017. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat. Genet. 49:659–65 [Google Scholar]
  124. Cinelli M, Sun Y, Best K, Heather JM, Reich-Zeliger S. 124.  et al. 2017. Feature selection using a one dimensional naive Bayes’ classifier increases the accuracy of support vector machine classification of CDR3 repertoires. Bioinformatics 33:951–55 [Google Scholar]
  125. Bolen CR, Rubelt F, Vander Heiden JA, Davis MM. 125.  2017. The Repertoire Dissimilarity Index as a method to compare lymphocyte receptor repertoires. BMC Bioinform 18:155 [Google Scholar]
  126. Angermueller C, Parnamaa T, Parts L, Stegle O. 126.  2016. Deep learning for computational biology. Mol. Syst. Biol. 12:878 [Google Scholar]
  127. Greiff V, Weber CR, Palme J, Bodenhofer U, Miho E. 127.  et al. 2017. Learning the high-dimensional immunogenomic features that predict public and private antibody repertoires. J. Immunol. 199:2985–2997 [Google Scholar]
  128. Boutz DR, Horton AP, Wine Y, Lavinder JJ, Georgiou G, Marcotte EM. 128.  2014. Proteomic identification of monoclonal antibodies from serum. Anal. Chem. 86:4758–66 [Google Scholar]
  129. Glanville J, Huang H, Nau A, Hatton O, Wagar LE. 129.  et al. 2017. Identifying specificity groups in the T cell receptor repertoire. Nature 547:94–98 [Google Scholar]
  130. Dash P, Fiore-Gartland AJ, Hertz T, Wang GC, Sharma S. 130.  et al. 2017. Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature 547:89–93 [Google Scholar]
/content/journals/10.1146/annurev-immunol-042617-053238
Loading
/content/journals/10.1146/annurev-immunol-042617-053238
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error