Skip to main content
SpringerLink
Log in

Regulatory and IgE+ B Cells in Allergic Asthma

  • Protocol
  • First Online:
Regulatory B Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2270))

Abstract

Allergic asthma is triggered by inhalation of environmental allergens resulting in bronchial constriction and inflammation, which leads to clinical symptoms such as wheezing, coughing, and difficulty breathing. Asthmatic airway inflammation is initiated by inflammatory mediators released by granulocytic cells. However, the immunoglobulin E (IgE) antibody is necessary for the initiation of the allergic cascade, and IgE is produced and released exclusively by memory B cells and plasma cells. Acute allergen exposure has also been shown to increase IgE levels in the airways of patients diagnosed with allergic asthma; however, more studies are needed to understand local airway inflammation. Additionally, regulatory B cells (Bregs) have been shown to modulate IgE-mediated inflammatory processes in allergic asthma pathogenesis, particularly in mouse models of allergic airway disease. However, the levels and function of these IgE+ B cells and Bregs remain to be elucidated in human models of asthma. The overall objective for this chapter is to provide detailed methodological, and insightful technological advances to study the biology of B cells in allergic asthma pathogenesis. Specifically, we will describe how to investigate the frequency and function of IgE+ B cells and Bregs in allergic asthma, and the kinetics of these cells after allergen exposure in a human asthma model.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lotvall J, Akdis CA, Barcharier LB, Bjermer L, Casale TB, Custovic A, Lemanske RF Jr, Wardlaw AJ, Wenzel SE, Greenberger PA (2015) Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 127(2):355–360. https://doi.org/10.1016/j.jaci.2010.11.037

    Article  Google Scholar 

  2. Akdis CA, Akdis M (2015) Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organization Journal 8(1):17–17. https://doi.org/10.1186/s40413-015-0063-2

    Article  CAS  Google Scholar 

  3. Wills-Karp M (1999) Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 17(1):255–281. https://doi.org/10.1146/annurev.immunol.17.1.255

    Article  CAS  PubMed  Google Scholar 

  4. Wills-Karp M (2004) Interleukin-13 in asthma pathogenesis. Immunol Rev 202(1):175–190. https://doi.org/10.1111/j.0105-2896.2004.00215.x

    Article  CAS  PubMed  Google Scholar 

  5. Gauvreau GM, Evans MY (2007) Allergen inhalation challenge: a human model of asthma exacerbation. Contrib Microbiol 14:21–32. https://doi.org/10.1159/0000107052

    Article  PubMed  Google Scholar 

  6. Smith SG, Gauvreau GM (2007) IL-13 is a novel therapeutic target in allergic asthma. Expert Reviews in Clinical Immunology 3:671–675

    Article  CAS  Google Scholar 

  7. Nair P, O'Byrne PM (2016) Measuring eosinophils to make treatment decisions in asthma. Chest 150(3):485–487. https://doi.org/10.1016/j.chest.2016.07.009

    Article  PubMed  Google Scholar 

  8. Holgate S, Casale T, Wenzel S, Bousquet J, Deniz Y, Reisner C (2005) The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J Allergy Clin Immunol 115(3):459–465. https://doi.org/10.1016/j.jaci.2004.11.053

    Article  CAS  PubMed  Google Scholar 

  9. Oliveria JP, Salter BM, Phan S, Obminski CD, Munoz CE, Smith SG, Scime T, Watson RM, Sehmi R, Gauvreau GM (2017) Asthmatic subjects with allergy have elevated levels of IgE+ B cells in the airways. J Allergy Clin Immunol 140(2):590–593.e9. https://doi.org/10.1016/j.jaci.2016.12.981

    Article  CAS  PubMed  Google Scholar 

  10. Oliveria JP, Salter BM, MacLean J, Kotwal S, Smith A, Harris JM, Scheerens H, Sehmi R, Gauvreau GM (2017) Increased IgE+ B cells in sputum, but not blood, bone marrow, or tonsils, after inhaled allergen challenge in subjects with asthma. Am J Respir Crit Care Med 196(1):107–109. https://doi.org/10.1164/rccm.201611-2274LE

    Article  CAS  PubMed  Google Scholar 

  11. Gauvreau GM, Arm JP, Boulet LP, Leigh R, Cockcroft DW, Davis BE, Mayers I, FitzGerald JM, Dahlen B, Killian KJ, Laviolette M, Carlsten C, Lazarinis N, Watson RM, Milot J, Swystun V, Bowen M, Hui L, Lantz AS, Meiser K, Maahs S, Lowe PJ, Skerjanec A, Drollmann A, O'Byrne PM (2016) Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses. J Allergy Clin Immunol 138(4):1051–1059. https://doi.org/10.1016/j.jaci.2016.02.027

    Article  CAS  PubMed  Google Scholar 

  12. Gauvreau GM, Harris JM, Boulet L-P, Scheerens H, Fitzgerald JM, Putnam WS, Cockcroft DW, Davis BE, Leigh R, Zheng Y, Dahlén B, Wang Y, Maciuca R, Mayers I, Liao XC, Wu LC, Matthews JG, O'Byrne PM (2014) Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production. Sci Transl Med 6(243):243ra85. https://doi.org/10.1126/scitranslmed.3008961

    Article  CAS  PubMed  Google Scholar 

  13. Maurer M, Giménez-Arnau AM, Sussman G, Metz M, Baker DR, Bauer A, Bernstein JA, Brehler R, Chu C-Y, Chung W-H, Danilycheva I, Grattan C, Hébert J, Katelaris C, Makris M, Meshkova R, Savic S, Sinclair R, Sitz K, Staubach P, Wedi B, Löffler J, Barve A, Kobayashi K, Hua E, Severin T, Janocha R (2019) Ligelizumab for chronic spontaneous Urticaria. N Engl J Med 381(14):1321–1332. https://doi.org/10.1056/NEJMoa1900408

    Article  CAS  PubMed  Google Scholar 

  14. Monson NL (2008) The natural history of B cells. Curr Opin Neurol 21(Suppl 1):S3–S8. https://doi.org/10.1097/01.wco.0000313358.53553.c7

    Article  CAS  PubMed  Google Scholar 

  15. Matsushita T, Yanaba K (2008) Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Investig 118(10):3420–3430. https://doi.org/10.1172/JCI36030

    Article  CAS  PubMed  Google Scholar 

  16. Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, Sato S, Tedder TF, Fujimoto M (2010) Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol 184(9):4801–4809. https://doi.org/10.4049/jimmunol.0902385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jurlander J, Lai CF, Tan J, Chou CC, Geisler CH, Schriber J, Blumenson LE, Narula SK, Baumann H, Ma C (1997) Characterization of interleukin-10 receptor expression on B-cell chronic lymphocytic leukemia cells. Blood 89(11):4146–4152

    Article  CAS  Google Scholar 

  18. Balkwill F, Montfort A, Capasso M (2013) B regulatory cells in cancer. Trends Immunol 34(4):169–173. https://doi.org/10.1016/j.it.2012.10.007

    Article  CAS  PubMed  Google Scholar 

  19. Hulse KE, Norton JE, Suh L, Zhong Q, Mahdavinia M, Simon P, Kern RC, Conley DB, Chandra RK, Tan BK, Peters AT, Grammer LC, Harris KE, Carter RG, Kato A, Schleimer RP (2013) Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression. Journal of Allergy and Clinical Immunology 131(4):1075–1083.e1077. https://doi.org/10.1016/j.jaci.2013.01.043

    Article  CAS  Google Scholar 

  20. Dullaers M, De Bruyne R, Ramadani F, Gould HJ, Gevaert P, Lambrecht BN (2012) The who, where, and when of IgE in allergic airway disease. J Allergy Clin Immunol 129(3):635–645. https://doi.org/10.1016/j.jaci.2011.10.029

    Article  CAS  PubMed  Google Scholar 

  21. Oettgen HC, Geha RS (2001) IgE regulation and roles in asthma pathogenesis. J Allergy Clin Immunol 107(3):429–440. https://doi.org/10.1067/mai.2001.113759

    Article  CAS  PubMed  Google Scholar 

  22. Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8(3):205–217. https://doi.org/10.1038/nri2273

    Article  CAS  PubMed  Google Scholar 

  23. Lundy SK, aa B, Martens TF, Lukacs NW (2005) Deficiency of regulatory B cells increases allergic airway inflammation. Inflamm Res 54(12):514–521. https://doi.org/10.1007/s00011-005-1387-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Amu S, Saunders SP, Kronenberg M, Mangan NE, Atzberger A, Fallon PG (2010) Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. Journal of Allergy and Clinical Immunology 125(5):1114–1124.e1118. https://doi.org/10.1016/j.jaci.2010.01.018

    Article  CAS  Google Scholar 

  25. Kato A, Hulse KE, Tan BK, Schleimer RP (2013) B-lymphocyte lineage cells and the respiratory system. J Allergy Clin Immunol 131(4):933–957. https://doi.org/10.1016/j.jaci.2013.02.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pieper K, Grimbacher B, Eibel H (2013) B-cell biology and development. J Allergy Clin Immunol 131(Fig 1):959–971. https://doi.org/10.1016/j.jaci.2013.01.046

    Article  CAS  PubMed  Google Scholar 

  27. Hagman J, Lukin K (2006) Transcription factors drive B cell development. Curr Opin Immunol 18(2):127–134. https://doi.org/10.1016/j.coi.2006.01.007

    Article  CAS  PubMed  Google Scholar 

  28. Vadasz Z, Toubi E (2014) The many faces of B regulatory cells. Isr Med Assoc J 16(10):631–633

    PubMed  Google Scholar 

  29. van der Vlugt LEPM, Mlejnek E, Ozir-Fazalalikhan A, Janssen Bonas M, Dijksman TR, Labuda La, Schot R, Guigas B, Möller GM, Hiemstra PS, Yazdanbakhsh M, Smits HH (2014) CD24(hi)CD27(+) B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide. Clin Exp Allergy 44 (4):517–528. https://doi.org/10.1111/cea.12238

  30. Perez-Andres M, Paiva B, Nieto WG, Caraux A, Schmitz A, Almeida J, Vogt RF, Marti GE, Rawstron AC, Van Zelm MC, JJM VD, Johnsen HE, Klein B, Orfao A (2010) Human peripheral blood B-cell compartments: a crossroad in B-cell traffic. Cytometry Part B, Clinical Cytometry 78(Suppl 1):S47–S60. https://doi.org/10.1002/cyto.b.20547

    Article  CAS  PubMed  Google Scholar 

  31. Samitas K, Lötvall J, Bossios A (2010) B cells: from early development to regulating allergic diseases. Arch Immunol Ther Exp 58(3):209–225. https://doi.org/10.1007/s00005-010-0073-2

    Article  Google Scholar 

  32. Stavnezer J, Guikema JEJ, Schrader CE (2008) Mechanism and regulation of class switch recombination. Annu Rev Immunol 26:261–292. https://doi.org/10.1146/annurev.immunol.26.021607.090248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hussaarts L, van der Vlugt LEPM, Yazdanbakhsh M, Smits HH (2011) Regulatory B-cell induction by helminths: implications for allergic disease. J Allergy Clin Immunol 128(4):733–739. https://doi.org/10.1016/j.jaci.2011.05.012

    Article  CAS  PubMed  Google Scholar 

  34. Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18(5):693–704. https://doi.org/10.1038/nm.2755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Pol MAVD, Lutter R, Ree RVV, Zee JSVD, Van De Pol MA, Van Ree R, van der Zee JS (2012) Increase in allergen-specific IgE and ex vivo Th2 responses after a single bronchial challenge with house dust mite in allergic asthmatics. Allergy: European. J Allergy Clin Immunol 67(8):67–73. https://doi.org/10.1111/j.1398-9995.2011.02722.x

    Article  CAS  Google Scholar 

  36. Wilson DR, Merrett TG, Varga EM, Smurthwaite L, Gould HJ, Kemp M, Hooper J, Till SJ, Durham SR (2002) Increases in allergen-specific IgE in BAL after segmental allergen challenge in atopic asthmatics. Am J Respir Crit Care Med 165(1):22–26. https://doi.org/10.1164/ajrccm.165.1.2010112

    Article  PubMed  Google Scholar 

  37. Nduati EW, Ng DHL, Ndungu FM, Gardner P, Urban BC, Langhorne J (2010) Distinct kinetics of memory B-cell and plasma-cell responses in peripheral blood following a blood-stage Plasmodium chabaudi infection in mice. PLoS One 5(11):e15007–e15007.

    Google Scholar 

  38. 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. Journal of Allergy and Clinical Immunology 124 (4):819–826.e814.

    Google Scholar 

  39. Chvatchko Y, Kosco-Vilbois MH, Herren S, Lefort J, Bonnefoy JY (1996) Germinal center formation and local immunoglobulin E (IgE) production in the lung after an airway antigenic challenge. J Exp Med 184(6):2353–2360. https://doi.org/10.1084/jem.184.6.2353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wong KJ, Timbrell V, Xi Y, Upham JW, Collins AM, Davies JM (2015) IgE+ B cells are scarce, but allergen-specific B cells with a memory phenotype circulate in patients with allergic rhinitis. Allergy 70(4):420–428. https://doi.org/10.1111/all.12563

    Article  CAS  PubMed  Google Scholar 

  41. Katz SI, Parker D, Turk JL (1974) B-cell suppression of delayed hypersensitivity reactions. Nature 251(5475):550–551. https://doi.org/10.1038/251550a0

    Article  CAS  PubMed  Google Scholar 

  42. Neta R, Salvin SB (1974) Specific suppression of delayed hypersensitivity: the possible presence of a suppressor B cell in the regulation of delayed hypersensitivity. J Immunol 113(6):1716–1725

    CAS  PubMed  Google Scholar 

  43. Mauri C, Menon M (2015) The expanding family of regulatory B cells. Int Immunol 27(10):479–486. https://doi.org/10.1093/intimm/dxv038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wolf SD, Dittel BN, Hardardottir F, Janeway CA (1996) Experimental autoimmune encephalomyelitis induction in genetically B cell–deficient mice. J Exp Med 184(6):2271–2278. https://doi.org/10.1084/jem.184.6.2271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK (2002) Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16(2):219–230. https://doi.org/10.1016/s1074-7613(02)00274-1

    Article  CAS  PubMed  Google Scholar 

  46. Miyagaki T, Fujimoto M, Sato S (2015) Regulatory B cells in human inflammatory and autoimmune diseases: from mouse models to clinical research. Int Immunol 27(10):495–504. https://doi.org/10.1093/intimm/dxv026

    Article  CAS  PubMed  Google Scholar 

  47. Gauvreau GM, Hessel EM, Boulet L-P, Coffman RL, O'Byrne PM (2006) Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses. Am J Respir Crit Care Med 174(1):15–20. https://doi.org/10.1164/rccm.200601-057OC

    Article  CAS  PubMed  Google Scholar 

  48. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950. https://doi.org/10.1038/ni833

    Article  CAS  PubMed  Google Scholar 

  49. Mauri C, Gray D, Mushtaq N, Londei M (2003) Prevention of arthritis by interleukin 10–producing B cells. J Exp Med 197(4):489–501. https://doi.org/10.1084/jem.20021293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112(5):1570–1580. https://doi.org/10.1182/blood-2008-02-078071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fagraeus A (1948) The plasma cellular reaction and its relation to the formation of antibodies in vitro. J Immunol 58(1):1–13

    CAS  PubMed  Google Scholar 

  52. Jacob J, Kelsoe G, Rajewsky K, Weiss U (1991) Intraclonal generation of antibody mutants in germinal centres. Nature 354(6352):389–392. https://doi.org/10.1038/354389a0

    Article  CAS  PubMed  Google Scholar 

  53. Carter NA, Vasconcellos R, Rosser EC, Tulone C, Muñoz-Suano A, Kamanaka M, Ehrenstein MR, Flavell RA, Mauri C (2011) Mice lacking endogenous IL-10–producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol 186(10):5569–5579.

    Google Scholar 

  54. Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, Mauri C (2013) CD19+ CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Science Translational Medicine 5 (173):173ra23

    Google Scholar 

  55. Rosser EC, Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42(4):607–612. https://doi.org/10.1016/j.immuni.2015.04.005

    Article  CAS  PubMed  Google Scholar 

  56. Zhang Y, Eliav Y, S-u S, Schreiber TH, Podack ER, Tadmor T, Rosenblatt JD (2013) B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion. Cancer Immunol Immunother 62(1):87–99. https://doi.org/10.1111/j.1398-9995.2011.02610.x

    Article  CAS  PubMed  Google Scholar 

  57. Moldaver D, Larché M (2011) Immunotherapy with peptides. Allergy 66(6):784–791

    Article  CAS  Google Scholar 

  58. Larché M (2006) Peptide immunotherapy. Immunol Allergy Clin N Am 26(2):321–332. https://doi.org/10.1016/j.iac.2006.02.005

    Article  Google Scholar 

  59. Ca A, Akdis M (2011) Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 127(1):18–27.; quiz 28-19. https://doi.org/10.1016/j.jaci.2010.11.030

    Article  CAS  Google Scholar 

  60. Akdis M, Ca A (2014) Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol 133(3):621–631. https://doi.org/10.1016/j.jaci.2013.12.1088

    Article  CAS  PubMed  Google Scholar 

  61. van de Veen W, Stanic B, Yaman G, Wawrzyniak M, Söllner S, Akdis DG, Rückert B, Akdis CA, Akdis M (2013) IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol 131(4):1204–1212. https://doi.org/10.1016/j.jaci.2013.01.014

    Article  CAS  PubMed  Google Scholar 

  62. Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771–5777. https://doi.org/10.4049/jimmunol.180.9.5771

    Article  CAS  PubMed  Google Scholar 

  63. van de Veen W, Stanic B, Wirz OF, Jansen K, Globinska A, Akdis M (2016) Role of regulatory B cells in immune tolerance to allergens and beyond. J Allergy Clin Immunol 138(3):654–665. https://doi.org/10.1016/j.jaci.2016.07.006

    Article  CAS  PubMed  Google Scholar 

  64. Banchereau J, Pascual V, O'garra A (2012) From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol 13(10):925–931. https://doi.org/10.1038/ni.2406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Taylor A, Akdis M, Joss A, Akkoç T, Wenig R, Colonna M, Daigle I, Flory E, Blaser K, Akdis CA (2007) IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain—containing protein tyrosine phosphatase 1. Journal of Allergy and Clinical Immunology 120 (1):76–83.

    Google Scholar 

  66. Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor-β: the role of T regulatory cells. Immunology 117(4):433–442. https://doi.org/10.1111/j.1365-2567.2006.02321.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ito S, Ansari P, Sakatsume M, Dickensheets H, Vazquez N, Donnelly RP, Larner AC, Finbloom DS (1999) Interleukin-10 inhibits expression of both interferon alpha–and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood 93(5):1456–1463. https://doi.org/10.1182/blood.V93.5.1456

    Article  CAS  PubMed  Google Scholar 

  68. Akdis CA, Blesken T, Akdis M, Wüthrich B, Blaser K (1998) Role of interleukin 10 in specific immunotherapy. J Clin Invest 102(1):98–106. https://doi.org/10.1172/JCI2250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M (2008) Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy 63(11):1455–1463. https://doi.org/10.1111/j.1398-9995.2008.01774.x

    Article  CAS  PubMed  Google Scholar 

  70. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, Nelson M, Weber R, Bernstein DI, Blessing-Moore J, Khan DA, Lang DM, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D (2011) Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol 127(1 Suppl):S1–55. https://doi.org/10.1016/j.jaci.2010.09.034

    Article  PubMed  Google Scholar 

  71. Moore KW, de Waal Malefyt E, Coffman RL, O'Garra A (2001) Interleukin-10 and the Interleukin-10 receptor. Annu Rev Immunol 19:683–765. https://doi.org/10.1146/annurev.immunol.19.1.683

    Article  CAS  PubMed  Google Scholar 

  72. Thorburn AN, Hansbro PM (2010) Harnessing regulatory T cells to suppress asthma: from potential to therapy. Am J Respir Cell Mol Biol 43(5):511–519. https://doi.org/10.1165/rcmb.2009-0342TR

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chu K-H, Chiang B-L (2012) Regulatory T cells induced by mucosal B cells alleviate allergic airway hypersensitivity. Am J Respir Cell Mol Biol 46(5):651–659. https://doi.org/10.1165/rcmb.2011-0246OC

    Article  CAS  PubMed  Google Scholar 

  74. Mauri C, Bosma A (2012) Immune regulatory function of B cells. Annu Rev Immunol 30:221–241. https://doi.org/10.1146/annurev-immunol-020711-074934

    Article  CAS  PubMed  Google Scholar 

  75. Noh J, Choi WS, Noh G, Lee JH (2010) Presence of Foxp3-expressing CD19(+)CD5(+) B cells in human peripheral blood mononuclear cells: human CD19(+)CD5(+)Foxp3(+) regulatory B cell (Breg). Immune Network 10(6):247–249. https://doi.org/10.4110/in.2010.10.6.247

    Article  PubMed  PubMed Central  Google Scholar 

  76. Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, St Clair EW, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117(2):530–541. https://doi.org/10.1182/blood-2010-07-294249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. James LK, Bowen H, Calvert RA, Dodev TS, Shamji MH, Beavil AJ, McDonnell JM, Durham SR, Gould HJ (2012) Allergen specificity of IgG(4)-expressing B cells in patients with grass pollen allergy undergoing immunotherapy. Journal of Allergy and Clinical Immunology 130 (3):663–670.e663. https://doi.org/10.1016/j.jaci.2012.04.006

  78. Maseda D, Smith SH, DiLillo DJ, Bryant JM, Candando KM, Weaver CT, Tedder TF (2012) Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J Immunol 188(3):1036–1048. https://doi.org/10.4049/jimmunol.1102500

    Article  CAS  PubMed  Google Scholar 

  79. Noh J, Noh G, Lee SJ, Lee JH, Kim A, Kim HS, Choi WS (2012) Tolerogenic effects of interferon-gamma with induction of allergen-specific interleukin-10-producing regulatory B cell (Br1) changes in non-IgE-mediated food allergy. Cell Immunol 273(2):140–149. https://doi.org/10.1016/j.cellimm.2011.12.006

    Article  CAS  PubMed  Google Scholar 

  80. Noh J, Lee JH, Noh G, Bang SY, Kim HS, Choi WS, Cho S, Lee SS (2010) Characterisation of allergen-specific responses of IL-10-producing regulatory B cells (Br1) in cow Milk allergy. Cell Immunol 264(2):143–149. https://doi.org/10.1016/j.cellimm.2010.05.013

    Article  CAS  PubMed  Google Scholar 

  81. Noh J, Noh G, Kim HS, Kim AR, Choi WS, Ra K, Choi WS (2012) Allergen-specific responses of CD19(+)CD5(+)Foxp3(+) regulatory B cells (Bregs) and CD4(+)Foxp3(+) regulatory T cell (Tregs) in immune tolerance of cow milk allergy of late eczematous reactions. Cell Immunol 274(1–2):109–114. https://doi.org/10.1016/j.cellimm.2012.01.005

    Article  CAS  PubMed  Google Scholar 

  82. Leaker BR, Singh D, Lindgren S, Almqvist G, Eriksson L, Young B, O'Connor B (2019) Effects of the toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study. Respir Res 20(1):288–288. https://doi.org/10.1186/s12931-019-1252-2

    Article  PubMed  PubMed Central  Google Scholar 

  83. Ma L, Xiao X, Ma Y, Wu H, Qiu S, Li J, Yang P, Liu Z (2017) Effect of activation of toll-like receptor 7 in the inhibition of allergic asthma on a mouse model. J Trans Res 9(5):2143–2152

    CAS  Google Scholar 

  84. Campbell JD, Sa K, Kozy HM, Ja L, Sweetwood R, Chu M, Cunningham CR, Salamon H, Lloyd CM, Coffman RL, Hessel EM (2014) A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice. Thorax 1:565. https://doi.org/10.1136/thoraxjnl-2013-204605

    Article  Google Scholar 

  85. Singh A, Carson WF, Secor ER, La G, Ra F, Clark RB, Thrall RS, Schramm CM (2008) Regulatory role of B cells in a murine model of allergic airway disease. J Immunol 180(11):7318–7326. https://doi.org/10.4049/jimmunol.180.11.7318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Braza F, Chesne J, Durand M, Dirou S, Brosseau C, Mahay G, Cheminant M-A, Magnan A, Brouard S (2015) A regulatory CD 9+ B-cell subset inhibits HDM-induced allergic airway inflammation. Allergy 70(11):1421–1431. https://doi.org/10.1111/all.12697

    Article  CAS  PubMed  Google Scholar 

  87. Noh G, Lee JH (2011) Regulatory B cells and allergic diseases. Allergy, Asthma Immunol Res 3(3):168–177. https://doi.org/10.4168/aair.2011.3.3.168

    Article  CAS  Google Scholar 

  88. Oliveria JP, El-Gammal AI, Yee M, Obminski CD, Scime TX, Watson RM, Howie K, O'Byrne PM, Sehmi R, Gauvreau GM (2018) Changes in regulatory B-cell levels in bone marrow, blood, and sputum of patients with asthma following inhaled allergen challenge. J Allergy Clin Immunol 141(4):1495. https://doi.org/10.1016/j.jaci.2017.11.013

    Article  PubMed  Google Scholar 

  89. Yanaba K, Bouaziz J-DD, Haas KM, Poe JC, Fujimoto M, Tedder TF (2008) A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28(5):639–650. https://doi.org/10.1016/j.immuni.2008.03.017

    Article  CAS  Google Scholar 

  90. Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF, Tamaki K (2007) CD19 expression in B cells is important for suppression of contact hypersensitivity. Am J Pathol 171(2):560–570. https://doi.org/10.2353/ajpath.2007.061279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bosma A, Abdel-Gadir A, Isenberg DA, Jury EC, Mauri C (2012) Lipid-antigen presentation by CD1d+ B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36(3):477–490. https://doi.org/10.1016/j.immuni.2012.02.008

    Article  CAS  PubMed  Google Scholar 

  92. Liu F, Ji J, Li X, Li X, Xu J, Yue H, Zhao S, Fan H, Hou Y (2017) Decreased CD1d level is associated with CD86 over-expression in B cells from systemic lupus erythematosus. Acta Biochim Biophys Sin 49(4):328–337. https://doi.org/10.1093/abbs/gmx011

    Article  CAS  PubMed  Google Scholar 

  93. Chaudhry MS, Karadimitris A (2014) Role and regulation of CD1d in Normal and pathological B cells. J Immunol 193(10):4761–4768. https://doi.org/10.4049/jimmunol.1401805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Brutkiewicz RR (2006) CD1d ligands: the good, the bad, and the ugly. J Immunol 177(2):769–775. https://doi.org/10.4049/jimmunol.177.2.769

    Article  CAS  PubMed  Google Scholar 

  95. Pa B, Noreña LY, Flores-Borja F, Rawlings DJ, Da I, Ehrenstein MR, Mauri C (2010) CD19+CD24hiCD38hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32(1):129–140. https://doi.org/10.1016/j.immuni.2009.11.009

    Article  CAS  Google Scholar 

  96. Siewe B, Stapleton JT, Martinson J, Keshavarzian A, Kazmi N, Demarais PM, French AL, Landay A (2013) Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti-HIV CD8+ T cell function in vitro. J Leukoc Biol 93(5):811–818. https://doi.org/10.1189/jlb.0912436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nouël A, Simon Q, Jamin C, Pers J-O, Hillion S (2014) Regulatory B cells: an exciting target for future therapeutics in transplantation. Front Immunol 5:11. https://doi.org/10.3389/fimmu.2014.00011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Khoder A, Sarvaria A, Alsuliman A, Chew C, Sekine T, Cooper N, Mielke S, De Lavallade H, Muftuoglu M, Curbelo IF (2014) Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD. Blood 124 (13):2034–2045.

    Google Scholar 

  99. Masson a d, Bouaziz JD, Le Buanec H, Robin M, O'Meara a PN, Rybojad M, Hau E, Monfort JB, Branchtein M, Michonneau D, Dessirier V, Sicre de Fontbrune F, Bergeron a IR, Dhedin N, Bengoufa D, Peffault de Latour R, Xhaard a BM, Bensussan a SG (2015) CD24hiCD27+ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease. Blood 125:1830. https://doi.org/10.1182/blood-2014-09-599159

    Article  CAS  PubMed  Google Scholar 

  100. Ray A, Wang L, Dittel BN (2015) IL-10-independent regulatory B-cell subsets and mechanisms of action. Int Immunol 27(10):531–536. https://doi.org/10.1093/intimm/dxv033

    Article  CAS  PubMed  Google Scholar 

  101. Lindner S, Dahlke K, Sontheimer K, Hagn M, Kaltenmeier C, Barth TF, Beyer T, Reister F, Fabricius D, Lotfi R (2013) Interleukin 21–induced granzyme B–expressing B cells infiltrate tumors and regulate T cells. Cancer Res 73(8):2468–2479. https://doi.org/10.1158/0008-5472.CAN-12-3450

    Article  CAS  PubMed  Google Scholar 

  102. Saze Z, Schuler PJ, Hong C-S, Cheng D, Jackson EK, Whiteside TL (2013) Adenosine production by human B cells and B cell–mediated suppression of activated T cells. Blood 122(1):9–18. https://doi.org/10.1182/blood-2013-02-482406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhang H-P, Wu Y, Liu J, Jiang J, Geng X-R, Yang G, Mo L, Liu Z-Q, Liu Z-G, Yang P-C (2013) TSP1-producing B cells show immune regulatory property and suppress allergy-related mucosal inflammation. Sci Rep 3:3345. https://doi.org/10.1038/srep03345

    Article  PubMed  PubMed Central  Google Scholar 

  104. Pepys J (1975) New tests to assess lung function. inhalation challenge tests in asthma. The New England Journal of Medicine 293(15):758–759. https://doi.org/10.1056/NEJM197510092931507

    Article  CAS  PubMed  Google Scholar 

  105. Hendrick DJ, Davies RJ, D'Souza MF, Pepys J (1975) An analysis of skin prick test reactions in 656 asthmatic patients. Thorax 30(1):2–8. https://doi.org/10.1136/thx.30.1.2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Clarke CW, Mitchell J, Nunn AJ, Pepys J (1982) Reproducibility of prick skin tests to five allergens. Clin Allergy 12(1):1–8. https://doi.org/10.1111/j.1365-2222.1982.tb03120.x

    Article  CAS  PubMed  Google Scholar 

  107. Bousquet J, Clark TJH, Hurd S, Khaltaev N, Lenfant C, O'Byrne P, Sheffer A (2007) GINA guidelines on asthma and beyond. Allergy 62(2):102–112. https://doi.org/10.1111/j.1398-9995.2006.01305.x

    Article  CAS  PubMed  Google Scholar 

  108. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J (2005) Standardisation of spirometry. Eur Respir J 26(2):319–338. https://doi.org/10.1183/09031936.05.00034805

    Article  CAS  PubMed  Google Scholar 

  109. Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE (1977) Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 7(3):235–243. https://doi.org/10.1111/j.1365.2222.1977.tb01448

    Article  CAS  PubMed  Google Scholar 

  110. O'Byrne PM, Dolovich J, Hargreave FE (1987) Late asthmatic responses. Am Rev Respir Dis 136(3):740–751. https://doi.org/10.1164/ajrccm/136.3.740

    Article  CAS  PubMed  Google Scholar 

  111. Diamant Z, Gauvreau GM, Cockcroft DW, Boulet LPP, Sterk PJ, de Jongh FHC, Dahlén B, O’Byrne PM (2013) Inhaled allergen bronchoprovocation tests. The Journal of Allergy and Clinical Immunology 132 (5):1045–1055.e1046. https://doi.org/10.1016/j.jaci.2013.08.023

  112. Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE (1996) Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med 154(2 Pt 1):308–317. https://doi.org/10.1164/ajrccm.154.2.8756799

    Article  CAS  PubMed  Google Scholar 

  113. Sohani ZN, Strinich TX, Watson B, Smith SG, Torek A, Howie KJ, Gauvreau GM (2011) Reproducibility of sputum differential cell counts is not affected by squamous epithelial cells. J Asthma 48(9):952–956. https://doi.org/10.3109/02770903.2011.617477

    Article  PubMed  Google Scholar 

  114. Kleinjan A, Vinke JG, Severijnen LWFM, Fokkens WJ (2000) Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients. Eur Respir J 15(3):491–497. https://doi.org/10.1034/j.1399-3003.2000.15.11.x

    Article  CAS  PubMed  Google Scholar 

  115. Zürcher AW, Derer T, Lang AB, Stadler BM (1996) Culture and IgE synthesis of nasal B cells. Int Arch Allergy Immunol 111 (1):77–82. doi:https://doi.org/10.1159/000237349

  116. Kamekura R, Shigehara K, Miyajima S, Jitsukawa S, Kawata K, Yamashita K, Nagaya T, Kumagai A, Sato A, Matsumiya H, Ogasawara N, Seki N, Takano K, Kokai Y, Takahashi H, Himi T, Ichimiya S (2015) Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma. Clin Immunol 158(2):204–211. https://doi.org/10.1016/j.clim.2015.02.016

    Article  CAS  PubMed  Google Scholar 

  117. Natarajan P, Singh a MNJT, Secor ER, La G, Thrall RS, Schramm CM (2012) Regulatory B cells from hilar lymph nodes of tolerant mice in a murine model of allergic airway disease are CD5+, express TGF-β, and co-localize with CD4+Foxp3+ T cells. Mucosal Immunol 5(6):691–701. https://doi.org/10.1038/mi.2012.42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Hoh RA, Joshi SA, Liu Y, Wang C, Roskin KM, Lee J-Y, Pham T, Looney TJ, Jackson KJL, Dixit VP, King J, Lyu S-C, Jenks J, Hamilton RG, Nadeau KC, Boyd SD (2016) Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol 137(1):157–167. https://doi.org/10.1016/j.jaci.2015.05.029

    Article  CAS  PubMed  Google Scholar 

  119. Yao Y, Liu R, Shin MS, Trentalange M, Allore H, Nassar A, Kang I, Pober JS, Montgomery RR (2014) CyTOF supports efficient detection of immune cell subsets from small samples. J Immunol Methods 415:1–5. https://doi.org/10.1016/j.jim.2014.10.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Proserpio V, Mahata B (2016) Single-cell technologies to study the immune system. Immunology 147(2):133–140. https://doi.org/10.1111/imm.12553

    Article  CAS  PubMed  Google Scholar 

  121. Bendall SC, Simonds EF, Qiu P, Amir E-aD, Krutzik PO, Finck R, Bruggner RV, Melamed R, Trejo A, Ornatsky OI, Balderas RS, Plevritis SK, Sachs K, Pe D, Tanner SD, Nolan GP (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332(6030):687–696. https://doi.org/10.1126/science.1198704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK (2012) A deep profiler's guide to cytometry. Trends Immunol 33(7):323–332. https://doi.org/10.1016/j.it.2012.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Bodenmiller B, Zunder ER, Finck R, Chen TJ, Savig ES, Bruggner RV, Simonds EF, Bendall SC, Sachs K, Krutzik PO, Nolan GP (2012) Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators. Nat Biotechnol 30(9):858–867. https://doi.org/10.1038/nbt.2317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Qiu P, Simonds EF, Bendall SC, Gibbs KD, Bruggner RV, Linderman MD, Sachs K, Nolan GP, Plevritis SK (2011) Extracting a cellular hierarchy from high-dimensional cytometry data with SPADE. Nat Biotechnol 29(10):886–891. https://doi.org/10.1038/nbt.1991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Gaudilliere B, Fragiadakis GK, Bruggner RV, Nicolau M, Finck R, Tingle M, Silva J, Ganio EA, Yeh CG, Maloney WJ, Huddleston JI, Goodman SB, Davis MM, Bendall SC, Fantl WJ, Angst MS, Nolan GP (2014) Clinical recovery from surgery correlates with single-cell immune signatures. Science Translational Medicine 6 (255):255ra131-255ra131.

    Google Scholar 

  126. Bendall SC, Nolan GP (2012) From single cells to deep phenotypes in cancer. Nat Biotechnol 30(7):639–647. https://doi.org/10.1038/nbt.2283

    Article  CAS  PubMed  Google Scholar 

  127. Glass DR, Tsai AG, Oliveria JP, Hartmann FJ, Kimmey SC, Calderon AA, Borges L, Glass MC, Wagar LE, Davis MM, Bendall SC (2020) An integrated multi-omic single-cell atlas of human B cell identity. Immunity 53 (1): 217-232.e5. https://doi.org/10.1016/j.immuni.2020.06.013

  128. Kimmey SC, Borges L, Baskar R, Bendall SC (2019) Parallel analysis of tri-molecular biosynthesis with cell identity and function in single cells. Nat Commun 10(1):1185–1185. https://doi.org/10.1038/s41467-019-09128-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hartmann FJ, Bendall SC (2019) Immune monitoring using mass cytometry and related high-dimensional imaging approaches. Nat Rev Rheumatol 16:87. https://doi.org/10.1038/s41584-019-0338-z

    Article  PubMed  Google Scholar 

  130. Hartmann FJ, Babdor J, Gherardini PF, Amir EAD, Jones K, Sahaf B, Marquez DM, Krutzik P, O'Donnell E, Sigal N, Maecker HT, Meyer E, Spitzer MH, Bendall SC (2019) Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy. Cell reports 28 (3):819–831.e814.

    Google Scholar 

  131. Hartmann FJ, Simonds EF, Vivanco N, Bruce T, Borges L, Nolan GP, Spitzer MH, Bendall SC (2019) Scalable Conjugation and Characterization of Immunoglobulins with Stable Mass Isotope Reporters for Single-Cell Mass Cytometry Analysis. Methods in molecular biology (Clifton, NJ) 1989:55–81.

    Google Scholar 

  132. Hartmann FJ, Simonds EF, Bendall SC (2018) A universal live cell barcoding-platform for multiplexed human single cell analysis. Sci Rep 8(1):10770–10770. https://doi.org/10.1038/s41598-018-28791-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Angelo M, Bendall SC, Finck R, Hale MB, Hitzman C, Borowsky AD, Levenson RM, Lowe JB, Liu SD, Zhao S, Natkunam Y, Nolan GP (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20(4):436–442. https://doi.org/10.1038/nm.3488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Keren L, Bosse M, Marquez D, Angoshtari R, Jain S, Varma S, Yang S-R, Kurian A, Van Valen D, West R, Bendall SC, Angelo M (2018) A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging. Cell 174 (6):1373–1387.e1319.

    Google Scholar 

  135. Keren L, Bosse M, Thompson S, Risom T, Vijayaragavan K, McCaffrey E, Marquez D, Angoshtari R, Greenwald NF, Fienberg H, Wang J, Kambham N, Kirkwood D, Nolan G, Montine TJ, Galli SJ, West R, Bendall SC, Angelo M (2019) MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure. Sci Adv 5 (10):eaax5851-eaax5851.

    Google Scholar 

  136. Zhao Y, Uduman M, Siu JHY, Tull TJ, Sanderson JD, Y-CB W, Zhou JQ, Petrov N, Ellis R, Todd K, Chavele K-M, Guesdon W, Vossenkamper A, Jassem W, D’Cruz DP, Fear DJ, John S, Scheel-Toellner D, Hopkins C, Moreno E, Woodman NL, Ciccarelli F, Heck S, Kleinstein SH, Bemark M, Spencer J (2018) Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue. Nat Commun 9(1):3857–3857. https://doi.org/10.1038/s41467-018-06089-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Kwak K, Quizon N, Sohn H, Saniee A, Manzella-Lapeira J, Holla P, Brzostowski J, Lu J, Xie H, Xu C, Spillane KM, Tolar P, Pierce SK (2018) Intrinsic properties of human germinal center B cells set antigen affinity thresholds. Sci Immunol 3 (29):eaau6598-eaau6598.

    Google Scholar 

  138. Oliveria JP (2020) Multiomic approaches to study B cells: sequencing, cytometry, imaging, and beyond. J Allergy Clin Immunol 146 (2): 456-457 https://doi.org/10.1016/j.jaci.2020.03.012

Download references

Acknowledgments

Our thanks to Ms. Vanessa Luk for editorial support. J.P.O. was supported by a Canadian Institutes of Health Research Postdoctoral Fellowship.

Author information

Authors and Affiliations

  1. School of Medicine, Department of Pathology, Stanford University, Stanford, CA, USA

    John Paul Oliveria

  2. Department of Medicine, Division of Respirology, McMaster University, Hamilton, ON, Canada

    John Paul Oliveria, Rita Agayby & Gail M. Gauvreau

Authors
  1. John Paul Oliveria
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rita Agayby
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gail M. Gauvreau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gail M. Gauvreau .

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Udine, Udine, Italy

    Francesca Mion

  2. Department of Medicine, University of Udine, Udine, Italy

    Silvia Tonon

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Oliveria, J.P., Agayby, R., Gauvreau, G.M. (2021). Regulatory and IgE+ B Cells in Allergic Asthma. In: Mion, F., Tonon, S. (eds) Regulatory B Cells. Methods in Molecular Biology, vol 2270. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1237-8_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1237-8_21

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1236-1

  • Online ISBN: 978-1-0716-1237-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation