Abstract
B cells are key players in the mechanisms underlying allergic sensitization, allergic reactions, and tolerance to allergens. Allergen-specific immune responses are initiated when peptide:MHCII complexes on dendritic cells are recognized by antigen-specific receptors on T cells followed by interactions between costimulatory molecules on the surfaces of B and T cells. In the presence of IL-4, such T-B cell interactions result in clonal expansion and isotype class-switching to IgE in B cells, which will further differentiate into either memory B cells or PCs. Allergic reactions are then triggered upon cross-linking of IgE-FcɛRI complexes on basophils and mast cells, leading to cell degranulation and the release of pro-inflammatory mediators.
Mechanisms underlying effective allergen-specific immunotherapy (AIT) involve the induction of Tregs and the secretion of blocking IgG4 antibodies, which together mediate the onset and maintenance of immune tolerance towards non-hazardous environmental antigens. However, the importance of regulatory B cells (Breg) for tolerance induction during AIT has gained more attention lately. Studies in grass pollen- and house dust mite-allergic patients undergoing SCIT reported increased frequencies of IL-10+ Breg cells and a positive correlation between their number and the improvement of clinical symptoms. Thus, Breg are emerging as biomarkers for monitoring tolerance to allergens under natural exposure conditions and during AIT. Further research on the role of other anti-inflammatory cytokines secreted by Breg will help to understand their role in disease development and tolerance induction.
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Acharya M, Borland G, Edkins AL, Maclellan LM, Matheson J, Ozanne BW, Cushley W (2010) CD23/FcepsilonRII: molecular multi-tasking. Clin Exp Immunol 162:12–23
Achour A, Simon Q, Mohr A, Seite JF, Youinou P, Bendaoud B, Ghedira I, Pers JO, Jamin C (2017) Human regulatory B cells control the TFH cell response. J Allergy Clin Immunol 140:215–222
Akiba H, Oshima H, Takeda K, Atsuta M, Nakano H, Nakajima A, Nohara C, Yagita H, Okumura K (1999) CD28-independent costimulation of T cells by OX40 ligand and CD70 on activated B cells. J Immunol 162:7058–7066
Berthelot JM, Jamin C, Amrouche K, Le Goff B, Maugars Y, Youinou P (2013) Regulatory B cells play a key role in immune system balance. Joint Bone Spine 80:18–22
Boonpiyathad T, Meyer N, Moniuszko M, Sokolowska M, Eljaszewicz A, Wirz OF, Tomasiak-Lozowska MM, Bodzenta-Lukaszyk A, Ruxrungtham K, van de Veen W (2017) High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers. Allergy 72:407–415
Boonpiyathad T, van de Veen W, Wirz O, Sokolowska M, Ruckert B, Tan G, Sangasapaviliya A, Pradubpongsa P, Fuengthong R, Thantiworasit P, Sirivichayakul S, Ruxrungtham K, Akdis CA, Akdis M (2019) Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy. J Allergy Clin Immunol 143:1077–86 e10
Cyster JG, Allen CDC (2019) B cell responses: cell interaction dynamics and decisions. Cell 177:524–540
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 129:635–645
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 26:191–203
Geha RS, Jabara HH, Brodeur SR (2003) The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol 3:721–732
Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8:205–217
Gould HJ, Wu YB (2018) IgE repertoire and immunological memory: compartmental regulation and antibody function. Int Immunol 30:403–412
He JS, Meyer-Hermann M, Xiangying D, Zuan LY, Jones LA, Ramakrishna L, de Vries VC, Dolpady J, Aina H, Joseph S, Narayanan S, Subramaniam S, Puthia M, Wong G, Xiong H, Poidinger M, Urban JF, Lafaille JJ, Curotto de Lafaille MA (2013) The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. J Exp Med 210:2755–2771
He JS, Subramaniam S, Narang V, Srinivasan K, Saunders SP, Carbajo D, Wen-Shan T, Hidayah Hamadee N, Lum J, Lee A, Chen J, Poidinger M, Zolezzi F, Lafaille JJ, Curotto de Lafaille MA (2017) IgG1 memory B cells keep the memory of IgE responses. Nat Commun 8:641
Huber S, Lang R, Steiner M, Aglas L, Ferreira F, Wallner M, Hawranek T, Gadermaier G (2018) Does clinical outcome of birch pollen immunotherapy relate to induction of blocking antibodies preventing IgE from allergen binding? A pilot study monitoring responses during first year of AIT. Clin Transl Allergy 8:39
Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, Hall RP, Clair EWS, Tedder TF (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117:530–541
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ (2001) B-cell activation by armed helper T cells. In: Immunobiology: the immune system in health and disease, 5th edn. Garland Science, New York
Jimenez-Saiz R, Chu DK, Mandur TS, Walker TD, Gordon ME, Chaudhary R, Koenig J, Saliba S, Galipeau HJ, Utley A, King IL, Lee K, Ettinger R, Waserman S, Kolbeck R, Jordana M (2017) Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy. J Allergy Clin Immunol 140:1604–1615.e5
Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O (2005) Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 116:608–613
Kim HS, Kim AR, Kim DK, Kim HW, Park YH, Jang GH, Kim B, Park YM, You JS, Kim HS, Beaven MA, Kim YM, Choi WS (2015) Interleukin-10-producing CD5+ B cells inhibit mast cells during immunoglobulin E-mediated allergic responses. Sci Signal 8:ra28
Klein U, Dalla-Favera R (2008) Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol 8:22–33
Kouser L, Kappen J, Walton RP, Shamji MH (2017) Update on biomarkers to monitor clinical efficacy response during and post treatment in allergen immunotherapy. Curr Treat Options Allergy 4:43–53
Layhadi JA, Eguiluz-Gracia I, Shamji MH (2019) Role of IL-35 in sublingual allergen immunotherapy. Curr Opin Allergy Clin Immunol 19:12–17
LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112:1570–1580
Lin X, Wang X, Xiao F, Ma K, Liu L, Wang X, Xu D, Wang F, Shi X, Liu D, Zhao Y, Lu L (2019) IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjogren’s syndrome. Cell Mol Immunol 16:921–931
Liu J, Chen FH, Qiu SQ, Yang LT, Zhang HP, Liu JQ, Geng XR, Yang G, Liu ZQ, Li J, Liu ZG, Li HB, Yang PC (2016) Probiotics enhance the effect of allergy immunotherapy on regulating antigen specific B cell activity in asthma patients. Am J Transl Res 8:5256–5270
Lundy SK, Klinker MW (2014) Characterization and activity of Fas ligand producing CD5(+) B cells. Methods Mol Biol 1190:81–102
Medina F, Segundo C, Campos-Caro A, Gonzalez-Garcia I, Brieva JA (2002) The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression. Blood 99:2154–2161
Mielle J, Audo R, Hahne M, Macia L, Combe B, Morel J, Daien C (2018) IL-10 producing B cells ability to induce regulatory T cells is maintained in rheumatoid arthritis. Front Immunol 9:961
Moutsoglou DM, Dreskin SC (2016) B cells establish, but do not maintain, long-lived murine anti-peanut IgE(a). Clin Exp Allergy 46:640–653
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 264:143–149
Oracki SA, Walker JA, Hibbs ML, Corcoran LM, Tarlinton DM (2010) Plasma cell development and survival. Immunol Rev 237:140–159
Palomares O, Akdis M, Martin-Fontecha M, Akdis CA (2017) Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells. Immunol Rev 278:219–236
Pennati A, Ng S, Wu Y, Murphy JR, Deng J, Rangaraju S, Asress S, Blanchfield JL, Evavold B, Galipeau J (2016) Regulatory B cells induce formation of IL-10-expressing T cells in mice with autoimmune neuroinflammation. J Neurosci 36:12598–12610
Pieper K, Grimbacher B, Eibel H (2013) B-cell biology and development. J Allergy Clin Immunol 131:959–971
Reisinger J, Horak F, Pauli G, van Hage M, Cromwell O, Konig F, Valenta R, Niederberger V (2005) Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 116:347–354
Roth K, Oehme L, Zehentmeier S, Zhang Y, Niesner R, Hauser AE (2014) Tracking plasma cell differentiation and survival. Cytometry A 85:15–24
Samitas K, Lotvall J, Bossios A (2010) B cells: from early development to regulating allergic diseases. Arch Immunol Ther Exp 58:209–225
Saraiva M, O’Garra A (2010) The regulation of IL-10 production by immune cells. Nat Rev Immunol 10:170–181
Saunders SP, Ma EGM, Aranda CJ, Curotto de Lafaille MA (2019) Non-classical B cell memory of allergic IgE responses. Front Immunol 10:715
Schulke S (2018) Induction of interleukin-10 producing dendritic cells as a tool to suppress allergen-specific T helper 2 responses. Front Immunol 9:455
Shamji MH, Durham SR (2017) Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. J Allergy Clin Immunol 140:1485–1498
Shamji MH, Layhadi JA, Achkova D, Kouser L, Perera-Webb A, Couto-Francisco NC, Parkin RV, Matsuoka T, Scadding G, Ashton-Rickardt PG, Durham SR (2019a) Role of IL-35 in sublingual allergen immunotherapy. J Allergy Clin Immunol 143:1131–1142 e4
Shamji MH, Kappen J, Abubakar-Waziri H, Zhang J, Steveling E, Watchman S, Kouser L, Eifan A, Switzer A, Varricchi G, Marone G, Couto-Francisco NC, Calderon M, Durham SR (2019b) Nasal allergen-neutralizing IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy. J Allergy Clin Immunol 143:1067–1076
Talay O, Yan D, Brightbill HD, Straney EE, Zhou M, Ladi E, Lee WP, Egen JG, Austin CD, Xu M, Wu LC (2012) IgE(+) memory B cells and plasma cells generated through a germinal-center pathway. Nat Immunol 13:396–404
Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A, Kaufman DL (2001) Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J Immunol 167:1081–1089
van de Veen W (2017) The role of regulatory B cells in allergen immunotherapy. Curr Opin Allergy Clin Immunol 17:447–452
van de Veen W, Stanic B, Yaman G, Wawrzyniak M, Sollner S, Akdis DG, Ruckert 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 131:1204–1212
van der Neut Kolfschoten M, Schuurman J, Losen M, Bleeker WK, Martinez-Martinez P, Vermeulen E, den Bleker TH, Wiegman L, Vink T, Aarden LA, De Baets MH, van de Winkel JG, Aalberse RC, Parren PW (2007) Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science 317:1554–1557
van Ree R, Hummelshoj L, Plantinga M, Poulsen LK, Swindle E (2014) Allergic sensitization: host-immune factors. Clin Transl Allergy 4:12
Vinuesa CG, Linterman MA, Goodnow CC, Randall KL (2010) T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev 237:72–89
Vizzardelli C, Gindl M, Roos S, Mobs C, Nagl B, Zimmann F, Sexl V, Kenner L, Neunkirchner A, Zlabinger GJ, Pickl WF, Pfutzner W, Bohle B (2018) Blocking antibodies induced by allergen-specific immunotherapy ameliorate allergic airway disease in a human/mouse chimeric model. Allergy 73:851–861
Wortel CM, Heidt S (2017) Regulatory B cells: phenotype, function and role in transplantation. Transpl Immunol 41:1–9
Wu LC, Zarrin AA (2014) The production and regulation of IgE by the immune system. Nat Rev Immunol 14:247–259
Wypych TP et al (2018) Role of B cells in TH cell responses in a mouse model of asthma. J Allergy Clin Immunol 141(4):1395–1410
Zissler UM, Jakwerth CA, Guerth FM, Pechtold L, Aguilar-Pimentel JA, Dietz K, Suttner K, Piontek G, Haller B, Hajdu Z, Schiemann M, Schmidt-Weber CB, Chaker AM (2018) Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three year grass-pollen AIT. EBioMedicine 36:475–488
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Pointner, L.N., Ferreira, F., Aglas, L. (2021). B Cell Functions in the Development of Type I Allergy and Induction of Immune Tolerance. In: Traidl-Hoffmann, C., Zuberbier, T., Werfel, T. (eds) Allergic Diseases – From Basic Mechanisms to Comprehensive Management and Prevention . Handbook of Experimental Pharmacology, vol 268. Springer, Cham. https://doi.org/10.1007/164_2021_479
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