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Biology of IgE Production: IgE Cell Differentiation and the Memory of IgE Responses

  • Jin-Shu He
  • Sriram Narayanan
  • Sharrada Subramaniam
  • Wen Qi Ho
  • Juan J. Lafaille
  • Maria A. Curotto de LafailleEmail author
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 388)

Abstract

The generation of long-lived plasma cells and memory B cells producing high-affinity antibodies depends on the maturation of B cell responses in germinal centers. These processes are essential for long-lasting antibody-mediated protection against infections. IgE antibodies are important for defense against parasites and toxins and can also mediate anti-tumor immunity. However, high-affinity IgE is also the main culprit responsible for the manifestations of allergic disease, including life-threatening anaphylaxis . Thus, generation of high-affinity IgE must be tightly regulated. Recent studies of IgE B cell biology have unveiled two mechanisms that limit high-affinity IgE memory responses: First, B cells that have recently switched to IgE production are programmed to rapidly differentiate into plasma cells, and second, IgE germinal center cells are transient and highly apoptotic. Opposing these processes, we now know that germinal center-derived IgG B cells can switch to IgE production, effectively becoming IgE-producing plasma cells. In this chapter, we will discuss the unique molecular and cellular pathways involved in the generation of IgE antibodies.

Keywords

Class Switching Dark Zone Class Switch Recombination Switch Region Sequential Switching 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AID

Activation-induced cytidine deaminase

BCR

B cell receptor

CSR

Class switch recombination

EMPD

Extra membrane proximal domain

GC

Germinal center

LN

Lymph node

PC

Plasma cell

TLR

Toll-like receptor

Notes

Acknowledgments

MACL laboratory is supported by A*STAR-SIgN core funding and by the Joint Council Organization (JCO) grant 1431AFG104, Singapore. J.J. Lafaille laboratory is supported by the Multiple Sclerosis Society, a B Levine scholarship and the NIH. We wish to thank Dr Lucy Robinson of Insight Editing London for her assistance in the preparation of the text.

References

  1. Achatz G, Nitschke L, Lamers MC (1997) Effect of transmembrane and cytoplasmic domains of IgE on the IgE response. Science 276:409–411PubMedCrossRefGoogle Scholar
  2. Achatz-Straussberger G, Zaborsky N, Konigsberger S, Luger EO, Lamers M, Crameri R, Achatz G (2008) Migration of antibody secreting cells towards CXCL12 depends on the isotype that forms the BCR. Eur J Immunol 38:3167–3177PubMedCentralPubMedCrossRefGoogle Scholar
  3. Arimura Y, Ogimoto M, Mitomo K, Katagiri T, Yamamoto K, Volarevic S, Mizuno K, Yakura H (2001) CD45 is required for CD40-induced inhibition of DNA synthesis and regulation of c-Jun NH2-terminal kinase and p38 in BAL-17 B cells. J Biol Chem 276:8550–8556PubMedCrossRefGoogle Scholar
  4. Audzevich T, Pearce G, Breucha M, Gunal G, Jessberger R (2013) Control of the STAT6-BCL6 antagonism by SWAP-70 determines IgE production. J Immunol 190:4946–4955PubMedCrossRefGoogle Scholar
  5. Batista FD, Anand S, Presani G, Efremov DG, Burrone OR (1996) The two membrane isoforms of human IgE assemble into functionally distinct B cell antigen receptors. J Exp Med 184:2197–2205PubMedCentralPubMedCrossRefGoogle Scholar
  6. Borggrefe T, Keshavarzi S, Gross B, Wabl M, Jessberger R (2001) Impaired IgE response in SWAP-70-deficient mice. Eur J Immunol 31:2467–2475PubMedCrossRefGoogle Scholar
  7. Cameron L, Gounni AS, Frenkiel S, Lavigne F, Vercelli D, Hamid Q (2003) Sε Sμ and Sε Sγ switch circles in human nasal mucosa following ex vivo allergen challenge: evidence for direct as well as sequential class switch recombination. J Immunol 171:3816–3822PubMedCrossRefGoogle Scholar
  8. Coffman RL, Lebman DA, Rothman P (1993) Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol 54:229–270PubMedCrossRefGoogle Scholar
  9. Coker HA, Durham SR, Gould HJ (2003) Local somatic hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis patients. J Immunol 171:5602–5610PubMedCrossRefGoogle Scholar
  10. Curotto de Lafaille MA, Kutchukhidze N, Shen S, Ding Y, Yee H, Lafaille JJ (2008) Adaptive Foxp3 + regulatory T cell-dependent and -independent control of allergic inflammation. Immunity 29:114–126PubMedCrossRefGoogle Scholar
  11. de Vries JE, Punnonen J, Cocks BG, de Waal Malefyt R, Aversa G (1993) Regulation of the human IgE response by IL4 and IL13. Res Immunol 144:597–601PubMedCrossRefGoogle Scholar
  12. Doi T, Obayashi K, Kadowaki T, Fujii H, Koyasu S (2008) PI3K is a negative regulator of IgE production. Int Immunol 20:499–508PubMedCrossRefGoogle Scholar
  13. Drinkwater N, Cossins BP, Keeble AH, Wright M, Cain K, Hailu H, Oxbrow A, Delgado J, Shuttleworth LK, Kao MW et al (2014) Human immunoglobulin E flexes between acutely bent and extended conformations. Nat Struct Mol Biol 21:397–404PubMedCentralPubMedCrossRefGoogle Scholar
  14. Edwalds-Gilbert G, Veraldi KL, Milcarek C (1997) Alternative poly(A) site selection in complex transcription units: means to an end? Nucleic Acids Res 25:2547–2561PubMedCentralPubMedCrossRefGoogle Scholar
  15. Erazo A, Kutchukhidze N, Leung M, Christ AP, Urban JF Jr, Curotto de Lafaille MA, Lafaille JJ (2007) Unique maturation program of the IgE response in vivo. Immunity 26:191–203PubMedCentralPubMedCrossRefGoogle Scholar
  16. Faris M, Gaskin F, Geha RS, Fu SM (1993) Tyrosine phosphorylation defines a unique transduction pathway in human B cells mediated via CD40. Trans Assoc Am Phys 106:187–195PubMedGoogle Scholar
  17. Faris M, Gaskin F, Parsons JT, Fu SM (1994) CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein. J Exp Med 179:1923–1931PubMedCrossRefGoogle Scholar
  18. Finkelman FD, Katona IM, Urban JF Jr, Holmes J, Ohara J, Tung AS, Sample JV, Paul WE (1988) IL-4 is required to generate and sustain in vivo IgE responses. J immunol 141:2335–2341PubMedGoogle Scholar
  19. Finkelman FD, Holmes J, Katona IM, Urban JF Jr, Beckmann MP, Park LS, Schooley KA, Coffman RL, Mosmann TR, Paul WE (1990) Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol 8:303–333PubMedCrossRefGoogle Scholar
  20. Fukuoka A, Futatsugi-Yumikura S, Takahashi S, Kazama H, Iyoda T, Yoshimoto T, Inaba K, Nakanishi K, Yonehara S (2013) Identification of a novel type 2 innate immunocyte with the ability to enhance IgE production. Int Immunol 25:373–382PubMedCrossRefGoogle Scholar
  21. Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18:693–704PubMedCentralPubMedCrossRefGoogle Scholar
  22. Geha RS, Jabara HH, Brodeur SR (2003) The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol 3:721–732PubMedCrossRefGoogle Scholar
  23. Gevaert P, Nouri-Aria KT, Wu H, Harper CE, Takhar P, Fear DJ, Acke F, De Ruyck N, Banfield G, Kariyawasam HH et al (2013) Local receptor revision and class switching to IgE in chronic rhinosinusitis with nasal polyps. Allergy 68:55–63PubMedCrossRefGoogle Scholar
  24. Glatman Zaretsky A, 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 206:991–999PubMedCrossRefGoogle Scholar
  25. Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8:205–217PubMedCrossRefGoogle Scholar
  26. Hackney JA, Misaghi S, Senger K, Garris C, Sun Y, Lorenzo MN, Zarrin AA (2009) DNA targets of AID evolutionary link between antibody somatic hypermutation and class switch recombination. Adv Immunol 101:163–189PubMedCrossRefGoogle Scholar
  27. Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, Ye BH, Kvatyuk M, Pandolfi PP, Cattoretti G et al (1999) Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iε transcription and immunoglobulin E switching. Mol Cell Biol 19:7264–7275PubMedCentralPubMedGoogle Scholar
  28. Harris MB, Mostecki J, Rothman PB (2005) Repression of an interleukin-4-responsive promoter requires cooperative BCL-6 function. J Biol Chem 280:13114–13121PubMedCrossRefGoogle Scholar
  29. He JS, Meyer-Hermann M, Xiangying D, Zuan LY, Jones LA, Ramakrishna L, de Vries VC, Dolpady J, Aina H, Joseph S et al (2013) The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. J Exp Med 210:2755–2771PubMedCentralPubMedCrossRefGoogle Scholar
  30. Holdom MD, Davies AM, Nettleship JE, Bagby SC, Dhaliwal B, Girardi E, Hunt J, Gould HJ, Beavil AJ, McDonnell JM et al (2011) Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor FcεRI. Nat Struct Mol Biol 18:571–576PubMedCentralPubMedCrossRefGoogle Scholar
  31. Janssen E, Ozcan E, Liadaki K, Jabara HH, Manis J, Ullas S, Akira S, Fitzgerald KA, Golenbock DT, Geha RS (2014) TRIF signaling is essential for TLR4-driven IgE class switching. J immunol 192:2651–2658PubMedCrossRefGoogle Scholar
  32. Jung S, Siebenkotten G, Radbruch A (1994) Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes. J Exp Med 179:2023–2026PubMedCrossRefGoogle Scholar
  33. Karnowski A, Achatz-Straussberger G, Klockenbusch C, Achatz G, Lamers MC (2006) Inefficient processing of mRNA for the membrane form of IgE is a genetic mechanism to limit recruitment of IgE-secreting cells. Eur J Immunol 36:1917–1925PubMedCrossRefGoogle Scholar
  34. Kashiwada M, Levy DM, McKeag L, Murray K, Schroder AJ, Canfield SM, Traver G, Rothman PB (2010) IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching. Proc Natl Acad Sci USA 107:821–826PubMedCentralPubMedCrossRefGoogle Scholar
  35. Katona IM, Urban JF Jr, Finkelman FD (1988) The role of L3T4 + and Lyt-2 + T cells in the IgE response and immunity to Nippostrongylus brasiliensis. J immunol 140:3206–3211PubMedGoogle Scholar
  36. Katona IM, Urban JF Jr, Kang SS, Paul WE, Finkelman FD (1991) IL-4 requirements for the generation of secondary in vivo IgE responses. J Immunol 146:4215–4221PubMedGoogle Scholar
  37. Kinet JP (1999) The high-affinity IgE receptor (FcεRI): from physiology to pathology. Annu Rev Immunol 17:931–972PubMedCrossRefGoogle Scholar
  38. Lafaille JJ, Xiong H, Curotto de Lafaille MA (2012) On the differentiation of mouse IgE+ cells. Nat Immunol 13:623 author reply 623–624PubMedCrossRefGoogle Scholar
  39. Laffleur B, Denis-Lagache N, Peron S, Sirac C, Moreau J, Cogne M (2014) AID-induced remodeling of immunoglobulin genes and B cell fate. Oncotarget 5:1118–1131PubMedCentralPubMedGoogle Scholar
  40. Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A (2002) DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol 3:822–829PubMedCrossRefGoogle Scholar
  41. Loh RK, Jabara HH, Ren CL, Fu SM, Vercelli D, Geha RS (1995) Role of protein tyrosine kinases and phosphatases in isotype switching: crosslinking CD45 to CD40 inhibits IgE isotype switching in human B cells. Immunol Lett 45:99–106PubMedCrossRefGoogle Scholar
  42. Luger EO, Fokuhl V, Wegmann M, Abram M, Tillack K, Achatz G, Manz RA, Worm M, Radbruch A, Renz H (2009) Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge. J Allergy Clin Immunol 124:819–826 e814PubMedCrossRefGoogle Scholar
  43. Magri G, Miyajima M, Bascones S, Mortha A, Puga I, Cassis L, Barra CM, Comerma L, Chudnovskiy A, Gentile M et al (2014) Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat Immunol 15:354–364PubMedCentralPubMedCrossRefGoogle Scholar
  44. Mandler R, Finkelman FD, Levine AD, Snapper CM (1993) IL-4 induction of IgE class switching by lipopolysaccharide-activated murine B cells occurs predominantly through sequential switching. J Immunol 150:407–418PubMedGoogle Scholar
  45. Mao CS, Stavnezer J (2001) Differential regulation of mouse germline Ig γ1 and ε promoters by IL-4 and CD40. J Immunol 167:1522–1534PubMedCrossRefGoogle Scholar
  46. Meyer-Hermann M, Mohr E, Pelletier N, Zhang Y, Victora GD, Toellner KM (2012) A theory of germinal center B cell selection, division, and exit. Cell Rep 2:162–174PubMedCrossRefGoogle Scholar
  47. Mills FC, Thyphronitis G, Finkelman FD, Max EE (1992) Ig mu-epsilon isotype switch in IL-4-treated human B lymphoblastoid cells. Evidence for a sequential switch. J Immunol 149:1075–1085PubMedGoogle Scholar
  48. Mills FC, Mitchell MP, Harindranath N, Max EE (1995) Human Ig S gamma regions and their participation in sequential switching to IgE. J Immunol 155:3021–3036PubMedGoogle Scholar
  49. Mohrs K, Wakil AE, Killeen N, Locksley RM, Mohrs M (2005) A two-step process for cytokine production revealed by IL-4 dual-reporter mice. Immunity 23:419–429PubMedCentralPubMedCrossRefGoogle Scholar
  50. 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 102:553–563PubMedCrossRefGoogle Scholar
  51. Nojima T, Haniuda K, Moutai T, Matsudaira M, Mizokawa S, Shiratori I, Azuma T, Kitamura D (2011) In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo. Nat Commun 2:465PubMedCrossRefGoogle Scholar
  52. Oberndorfer I, Schmid D, Geisberger R, Achatz-Straussberger G, Crameri R, Lamers M, Achatz G (2006) HS1-associated protein X-1 interacts with membrane-bound IgE: impact on receptor-mediated internalization. J Immunol 177:1139–1145PubMedCrossRefGoogle Scholar
  53. Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A, Morse HC 3rd, Liu C, Schwartzberg PL, Leonard WJ (2002) A critical role for IL-21 in regulating immunoglobulin production. Sci 298:1630–1634CrossRefGoogle Scholar
  54. Pesu M, Aittomaki S, Takaluoma K, Lagerstedt A, Silvennoinen O (2002) p38 Mitogen-activated protein kinase regulates interleukin-4-induced gene expression by stimulating STAT6-mediated transcription. J Biol Chem 277:38254–38261PubMedCrossRefGoogle Scholar
  55. Poggianella M, Bestagno M, Burrone OR (2006) The extracellular membrane-proximal domain of human membrane IgE controls apoptotic signaling of the B cell receptor in the mature B cell line A20. J Immunol 177:3597–3605PubMedCrossRefGoogle Scholar
  56. Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G, de Waal Malefyt R, de Vries JE (1993) Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA 90:3730–3734PubMedCentralPubMedCrossRefGoogle Scholar
  57. Reinhardt RL, Liang HE, Locksley RM (2009) Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 10:385–393PubMedCentralPubMedCrossRefGoogle Scholar
  58. Rothman PB (2010) The transcriptional regulator NFIL3 controls IgE production. Trans Am Clin Climatol Assoc 121:156–171 discussion 171PubMedCentralPubMedGoogle Scholar
  59. Rothman P, Lutzker S, Cook W, Coffman R, Alt FW (1988) Mitogen plus interleukin 4 induction of C epsilon transcripts in B lymphoid cells. J Exp Med 168:2385–2389PubMedCrossRefGoogle Scholar
  60. Siebenkotten G, Esser C, Wabl M, Radbruch A (1992) The murine IgG1/IgE class switch program. Eur J Immunol 22:1827–1834PubMedCrossRefGoogle Scholar
  61. Smurthwaite L, Walker SN, Wilson DR, Birch DS, Merrett TG, Durham SR, Gould HJ (2001) Persistent IgE synthesis in the nasal mucosa of hay fever patients. Eur J Immunol 31:3422–3431PubMedCrossRefGoogle Scholar
  62. Snapper CM, Finkelman FD, Stefany D, Conrad DH, Paul WE (1988) IL-4 induces co-expression of intrinsic membrane IgG1 and IgE by murine B cells stimulated with lipopolysaccharide. J Immunol 141:489–498PubMedGoogle Scholar
  63. Sugai M, Gonda H, Kusunoki T, Katakai T, Yokota Y, Shimizu A (2003) Essential role of Id2 in negative regulation of IgE class switching. Nat Immunol 4:25–30PubMedCrossRefGoogle Scholar
  64. Suto A, Nakajima H, Hirose K, Suzuki K, Kagami S, Seto Y, Hoshimoto A, Saito Y, Foster DC, Iwamoto I (2002) Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4-stimulated B cells. Blood 100:4565–4573PubMedCrossRefGoogle Scholar
  65. Takhar P, Smurthwaite L, Coker HA, Fear DJ, Banfield GK, Carr VA, Durham SR, Gould HJ (2005) Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis. J Immunol 174:5024–5032PubMedCrossRefGoogle Scholar
  66. Takhar P, Corrigan CJ, Smurthwaite L, O’Connor BJ, Durham SR, Lee TH, Gould HJ (2007) Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma. J Allergy Clin Immunol 119:213–218PubMedCrossRefGoogle Scholar
  67. Talay O, Yan D, Brightbill HD, Straney EE, Zhou M, Ladi E, Lee WP, Egen JG, Austin CD, Xu M et al (2012) IgE+ memory B cells and plasma cells generated through a germinal-center pathway. Nat Immunol 13:396–404PubMedCrossRefGoogle Scholar
  68. Talay O, Yan D, Brightbill HD, Straney EE, Zhou M, Ladi E, Lee WP, Egen JG, Austin CD, Xu M et al (2013) Addendum: IgE+ memory B cells and plasma cells generated through a germinal-center pathway. Nat Immunol 14:1302–1304PubMedCrossRefGoogle Scholar
  69. Tarlinton DM (2008) Evolution in miniature: selection, survival and distribution of antigen reactive cells in the germinal centre. Immunol Cell Biol 86:133–138PubMedCrossRefGoogle Scholar
  70. Turqueti-Neves A, Otte M, Prazeres da Costa O, Hopken UE, Lipp M, Buch T, Voehringer D (2014) B-cell-intrinsic STAT6 signaling controls germinal center formation. Eur J Immunol 44:2130–2138PubMedCrossRefGoogle Scholar
  71. Venkitaraman AR, Williams GT, Dariavach P, Neuberger MS (1991) The B-cell antigen receptor of the five immunoglobulin classes. Nature 352:777–781PubMedCrossRefGoogle Scholar
  72. Victora GD, Nussenzweig MC (2012) Germinal centers. Annu Rev Immunol 30:429–457PubMedCrossRefGoogle Scholar
  73. Vieira P, Rajewsky K (1988) The half-lives of serum immunoglobulins in adult mice. Eur J Immunol 18:313–316PubMedCrossRefGoogle Scholar
  74. Vinuesa CG, Tangye SG, Moser B, Mackay CR (2005) Follicular B helper T cells in antibody responses and autoimmunity. Nat Rev Immunol 5:853–865PubMedCrossRefGoogle Scholar
  75. Wan T, Beavil RL, Fabiane SM, Beavil AJ, Sohi MK, Keown M, Young RJ, Henry AJ, Owens RJ, Gould HJ et al (2002) The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Nat Immunol 3:681–686PubMedCrossRefGoogle Scholar
  76. Wu LC, Zarrin AA (2014) The production and regulation of IgE by the immune system. Nat Rev Immunol 14:247–259PubMedCrossRefGoogle Scholar
  77. Xiong H, Curotto de Lafaille MA, Lafaille JJ (2012a) What is unique about the IgE response? Adv Immunol 116:113–141PubMedCrossRefGoogle Scholar
  78. Xiong H, Dolpady J, Wabl M, Curotto de Lafaille MA, Lafaille JJ (2012b) Sequential class switching is required for the generation of high affinity IgE antibodies. J Exp Med 209:353–364PubMedCentralPubMedCrossRefGoogle Scholar
  79. Yang Z, Sullivan BM, Allen CD (2012) Fluorescent in vivo detection reveals that IgE+ B Cells are restrained by an intrinsic cell fate predisposition. Immunity 36:857–872PubMedCrossRefGoogle Scholar
  80. Yang Z, Robinson MJ, Allen CD (2014) Regulatory constraints in the generation and differentiation of IgE-expressing B cells. Curr Opin Immunol 28:64–70PubMedCrossRefGoogle Scholar
  81. Yoshida K, Matsuoka M, Usuda S, Mori A, Ishizaka K, Sakano H (1990) Immunoglobulin switch circular DNA in the mouse infected with Nippostrongylus brasiliensis: evidence for successive class switching from mu to epsilon via gamma 1. Proc Natl Acad Sci USA 87:7829–7833PubMedCentralPubMedCrossRefGoogle Scholar
  82. Zhang K, Zhang L, Zhu D, Bae D, Nel A, Saxon A (2002) CD40-mediated p38 mitogen-activated protein kinase activation is required for immunoglobulin class switch recombination to IgE. J Allergy Clin Immunol 110:421–428PubMedCrossRefGoogle Scholar
  83. Zhang TT, Okkenhaug K, Nashed BF, Puri KD, Knight ZA, Shokat KM, Vanhaesebroeck B, Marshall AJ (2008) Genetic or pharmaceutical blockade of p110δ phosphoinositide 3-kinase enhances IgE production. J Allergy Clin Immunol 122:811–819 e812PubMedCrossRefGoogle Scholar
  84. Zhang TT, Makondo KJ, Marshall AJ (2012) p110delta phosphoinositide 3-kinase represses IgE switch by potentiating BCL6 expression. J Immunol 188:3700–3708PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Jin-Shu He
    • 1
  • Sriram Narayanan
    • 1
  • Sharrada Subramaniam
    • 1
    • 2
  • Wen Qi Ho
    • 1
  • Juan J. Lafaille
    • 3
  • Maria A. Curotto de Lafaille
    • 1
    Email author
  1. 1.Singapore Immunology Network (SIgN)Agency for Science, Technology and ResearchSingaporeSingapore
  2. 2.Nanyang Technological University, School of Biological SciencesSingaporeSingapore
  3. 3.Skirball Institute and Department of PathologyNew York University School of MedicineNew YorkUSA

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