Abstract
Clustering of the high-affinity receptor for immunoglobulin E (FcεRI ) through the interaction of receptor-bound immunoglobulin E (IgE ) antibodies with their cognate antigen is required to couple IgE antibody production to cellular responses and physiological consequences. IgE -induced responses through FcεRI are well known to defend the host against certain infectious agents and to lead to unwanted allergic responses to normally innocuous substances. However, the cellular and/or physiological response of individuals that produce IgE antibodies may be markedly different and such antibodies (even to the same antigenic epitope) can differ in their antigen-binding affinity. How affinity variation in the interaction of FcεRI -bound IgE antibodies with antigen is interpreted into cellular responses and how the local environment may influence these responses is of interest. In this chapter, we focus on recent advances that begin to unravel how FcεRI distinguishes differences in the affinity of IgE –antigen interactions and how such discrimination along with surrounding environmental stimuli can shape the (patho) physiological response.
The studies of the authors herein described were supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
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- BCR:
-
B cell receptor
- BTK:
-
Bruton’s tyrosine kinase
- CBMC:
-
Cord blood-derived mast cells
- DAG:
-
Diacylglycerol
- DNP:
-
Dinitrophenyl
- ERK:
-
Extracellular signal-regulated kinase
- FcεRI:
-
High-affinity receptor for immunoglobulin E
- FRAP:
-
Fluorescence recovery after photobleaching
- FSMC:
-
Fetal skin-derived mast cells
- GAB2:
-
GRB2-associated-binding protein 2
- GFP:
-
Green fluorescent protein
- GIRKs:
-
G-protein-coupled inwardly rectifying potassium channels
- GM-CSF:
-
Granulocyte macrophage colony-stimulating factor
- HC:
-
Highly cytokinergic
- HSA:
-
Human serum albumin
- IgE:
-
Immunoglobulin E
- IP3:
-
Inositol 1,4,5, triphosphate
- ITAM:
-
Immunoreceptor tyrosine-based activation motif
- ITIM:
-
Immunoreceptor tyrosine-based inhibitory motif
- JNK:
-
c-Jun N-terminal protein kinase
- LAT1:
-
Linker for activation of T cells
- LAT2:
-
Linker for activation of T cells family, member 2
- LIF:
-
Leukemia inhibitory factor
- LTC4:
-
Leukotriene C4
- MAP Kinase:
-
Mitogen-activated protein kinase
- MCP-1:
-
Monocyte chemoattractant protein-1
- MIP-1:
-
Macrophage inflammatory proteins-1
- MITF:
-
Microphthalmia transcription factor
- NFAT:
-
Nuclear factor of activated T cells
- PC:
-
Poorly cytokinergic
- PCA:
-
Passive cutaneous anaphylaxis
- PI3-K:
-
Phosphoinositide 3-kinase
- PIP:
-
Phosphatidylinositol 4,5 bisphosphate
- PKC:
-
Protein kinase C
- PLC:
-
Phospholipase C
- PTK:
-
Protein tyrosine kinase
- QD:
-
Quantum dot
- RBL-2H3:
-
Rat basophilic leukemia subclone-2H3
- STAT:
-
Signal transducer and activator of transcription
- Syk:
-
Spleen tyrosine kinase
- TIRF:
-
Total internal reflection fluorescence
- TLR:
-
Toll-like receptor
- TNF:
-
Tumor necrosis factor
- TRB3:
-
Tribbles homolog 3
- VEGF:
-
Vascular endothelial growth factor
References
Adachi S, Nakano T, Vliagoftis H, Metcalfe DD (1999) Receptor-mediated modulation of murine mast cell function by alpha-melanocyte stimulating hormone. J Immunol 163(6):3363–3368
Alm E, Bloom GD (1982) Cyclic nucleotide involvement in histamine release from mast cells–a reevaluation. Life Sci 30(3):213–218
Andrews NL, Pfeiffer JR, Martinez AM, Haaland DM, Davis RW, Kawakami T, Oliver JM, Wilson BS, Lidke DS (2009) Small, mobile FcεRI receptor aggregates are signaling competent. Immunity 31(3):469–479
Arock M, Zuany-Amorim C, Singer M, Benhamou M, Pretolani M (1996) Interleukin-10 inhibits cytokine generation from mast cells. Eur J Immunol 26(1):166–170
Avila M, Martinez-Juarez A, Ibarra-Sanchez A, Gonzalez-Espinosa C (2012) Lyn kinase controls TLR4-dependent IKK and MAPK activation modulating the activity of TRAF-6/TAK-1 protein complex in mast cells. Innate Immun 18(4):648–660
Bachelet I, Munitz A, Mankutad D, Levi-Schaffer F (2006) Mast cell costimulation by CD226/CD112 (DNAM-1/Nectin-2): a novel interface in the allergic process. J Biol Chem 281(37):27190–27196
Bachelet I, Munitz A, Moretta A, Moretta L, Levi-Schaffer F (2005) The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast cells. J Immunol 175(12):7989–7995
Barrow AD, Astoul E, Floto A, Brooke G, Relou IA, Jennings NS, Smith KG, Ouwehand W, Farndale RW, Alexander DR, Trowsdale J (2004) Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2. J Immunol 172(10):5838–5842
Birnbaumer L (2007) Expansion of signal transduction by G proteins. The second 15 years or so: from 3 to 16 alpha subunits plus betagamma dimers. Biochim Biophys Acta 1768(4):772–793
Bischoff SC (2007) Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7(2):93–104
Bissonnette EY, Befus AD (1997) Anti-inflammatory effect of β 2-agonists: inhibition of TNF-α release from human mast cells. J Allergy Clin Immunol 100(6 Pt 1):825–831
Bissonnette EY, Enciso JA, Befus AD (1997) TGF-β1 inhibits the release of histamine and tumor necrosis factor-α from mast cells through an autocrine pathway. Am J Respir Cell Mol Biol 16(3):275–282
Carroll-Portillo A, Spendier K, Pfeiffer J, Griffiths G, Li H, Lidke KA, Oliver JM, Lidke DS, Thomas JL, Wilson BS, Timlin JA (2010) Formation of a mast cell synapse: FcεRI membrane dynamics upon binding mobile or immobilized ligands on surfaces. J Immunol 184(3):1328–1338
Castells MC, Klickstein LB, Hassani K, Cumplido JA, Lacouture ME, Austen KF, Katz HR (2001) gp49B1-α(v)β3 interaction inhibits antigen-induced mast cell activation. Nat Immunol 2(5):436–442
Chaudhary A, Fresquez TM, Naranjo MJ (2007) Tyrosine kinase Syk associates with toll-like receptor 4 and regulates signaling in human monocytic cells. Immunol Cell Biol 85(3):249–256
Cherwinski HM, Murphy CA, Joyce BL, Bigler ME, Song YS, Zurawski SM, Moshrefi MM, Gorman DM, Miller KL, Zhang S, Sedgwick JD, Phillips JH (2005) The CD200 receptor is a novel and potent regulator of murine and human mast cell function. J Immunol 174(3):1348–1356
Cruse G, Kaur D, Yang W, Duffy SM, Brightling CE, Bradding P (2005) Activation of human lung mast cells by monomeric immunoglobulin E. Eur Respir J 25(5):858–863
Daeron M, Malbec O, Latour S, Arock M, Fridman WH (1995) Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest 95(2):577–585
Edwards LJ, Evavold BD (2011) T cell recognition of weak ligands: roles of signaling, receptor number, and affinity. Immunol Res 50(1):39–48
Erdei A, Andreev S, Pecht I (1995) Complement peptide C3a inhibits IgE-mediated triggering of rat mucosal mast cells. Int Immunol 7(9):1433–1439
Erdei A, Toth GK, Andrasfalvy M, Matko J, Bene L, Bajtay Z, Ischenko A, Rong X, Pecht I (1999) Inhibition of IgE-mediated triggering of mast cells by complement-derived peptides interacting with the Fc ε RI. Immunol Lett 68(1):79–82
Fehrenbach K, Port F, Grochowy G, Kalis C, Bessler W, Galanos C, Krystal G, Freudenberg M, Huber M (2007) Stimulation of mast cells via FcvarepsilonR1 and TLR2: the type of ligand determines the outcome. Mol Immunol 44(8):2087–2094
Feng C, Beller EM, Bagga S, Boyce JA (2006) Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses. Blood 107(8):3243–3250
Feoktistov I, Biaggioni I (1995) Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. J Clin Invest 96(4):1979–1986
Fewtrell C, Metzger H (1980) Larger oligomers of IgE are more effective than dimers in stimulating rat basophilic leukemia cells. J Immunol 125(2):701–710
Furuichi K, Rivera J, Isersky C (1985) The receptor for immunoglobulin E on rat basophilic leukemia cells: effect of ligand binding on receptor expression. Proc Natl Acad Sci USA 82(5):1522–1525
Gao ZG, Wei Q, Jayasekara MP, Jacobson KA (2012) The role of P2Y(14) and other P2Y receptors in degranulation of human LAD2 mast cells. Purinergic Signal 9(1):31–40
Gebhardt T, Sellge G, Lorentz A, Raab R, Manns MP, Bischoff SC (2002) Cultured human intestinal mast cells express functional IL-3 receptors and respond to IL-3 by enhancing growth and IgE receptor-dependent mediator release. Eur J Immunol 32(8):2308–2316
Gilchrest H, Cheewatrakoolpong B, Billah M, Egan RW, Anthes JC, Greenfeder S (2003) Human cord blood-derived mast cells synthesize and release I-309 in response to IgE. Life Sci 73(20):2571–2581
Gilfillan AM, Beaven MA (2011) Regulation of mast cell responses in health and disease. Crit Rev Immunol 31(6):475–529
Gomez G, Gonzalez-Espinosa C, Odom S, Baez G, Cid ME, Ryan JJ, Rivera J (2005a) Impaired FcεRI-dependent gene expression and defective eicosanoid and cytokine production as a consequence of Fyn deficiency in mast cells. J Immunol 175(11):7602–7610
Gomez G, Ramirez CD, Rivera J, Patel M, Norozian F, Wright HV, Kashyap MV, Barnstein BO, Fischer-Stenger K, Schwartz LB, Kepley CL, Ryan JJ (2005b) TGF-β 1 inhibits mast cell Fc ε RI expression. J Immunol 174(10):5987–5993
Gomez G, Nardone V, Lotfi-Emran S, Zhao W, Schwartz LB (2013) Intracellular adenosine inhibits IgE-dependent degranulation of human skin mast cells. J Clin Immunol 33(8):1349–1359
Gonzalez-Espinosa C, Odom S, Olivera A, Hobson JP, Martinez ME, Oliveira-Dos-Santos A, Barra L, Spiegel S, Penninger JM, Rivera J (2003) Preferential signaling and induction of allergy-promoting lymphokines upon weak stimulation of the high affinity IgE receptor on mast cells. J Exp Med 197(11):1453–1465
Gri G, Piconese S, Frossi B, Manfroi V, Merluzzi S, Tripodo C, Viola A, Odom S, Rivera J, Colombo MP, Pucillo CE (2008) CD4 + CD25 + regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 29(5):771–781
Grodzki AC, Moon KD, Berenstein EH, Siraganian RP (2009) FcεRI-induced activation by low antigen concentrations results in nuclear signals in the absence of degranulation. Mol Immunol 46(13):2539–2547
Guthmann MD, Tal M, Pecht I (1995) A new member of the C-type lectin family is a modulator of the mast cell secretory response. Int Arch Allergy Immunol 107(1–3):82–86
Hitomi K, Tahara-Hanaoka S, Someya S, Fujiki A, Tada H, Sugiyama T, Shibayama S, Shibuya K, Shibuya A (2010) An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions. Nat Immunol 11(7):601–607
Hlavacek WS, Redondo A, Metzger H, Wofsy C, Goldstein B (2001) Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading. Proc Natl Acad Sci USA 98(13):7295–7300
Hong H, Kitaura J, Xiao W, Horejsi V, Ra C, Lowell CA, Kawakami Y, Kawakami T (2007) The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn. Blood 110(7):2511–2519
Horwood NJ, Page TH, McDaid JP, Palmer CD, Campbell J, Mahon T, Brennan FM, Webster D, Foxwell BM (2006) Bruton’s tyrosine kinase is required for TLR2 and TLR4-induced TNF, but not IL-6, production. J Immunol 176(6):3635–3641
Hsieh FH, Lam BK, Penrose JF, Austen KF, Boyce JA (2001) T helper cell type 2 cytokines coordinately regulate immunoglobulin E-dependent cysteinyl leukotriene production by human cord blood-derived mast cells: profound induction of leukotriene C(4) synthase expression by interleukin 4. J Exp Med 193(1):123–133
Hughes PJ, Holgate ST, Church MK (1984) Adenosine inhibits and potentiates IgE-dependent histamine release from human lung mast cells by an A2-purinoceptor mediated mechanism. Biochem Pharmacol 33(23):3847–3852
Isersky C, Taurog JD, Poy G, Metzger H (1978) Triggering of cultured neoplastic mast cells by antibodies to the receptor for IgE. J Immunol 121(2):549–558
Isersky C, Rivera J, Mims S, Triche TJ (1979) The fate of IgE bound to rat basophilic leukemia cells. J Immunol 122(5):1926–1936
Ishizaka T, Chang TH, Taggart M, Ishizaka K (1977) Histamine release from rat mast cells by antibodies against rat basophilic leukemia cell membrane. J Immunol 119(5):1589–1596
Ishizuka T, Kawasome H, Terada N, Takeda K, Gerwins P, Keller GM, Johnson GL, Gelfand EW (1998) Stem cell factor augments Fc ε RI-mediated TNF-α production and stimulates MAP kinases via a different pathway in MC/9 mast cells. J Immunol 161(7):3624–3630
Izawa K, Kitaura J, Yamanishi Y, Matsuoka T, Kaitani A, Sugiuchi M, Takahashi M, Maehara A, Enomoto Y, Oki T, Takai T, Kitamura T (2009) An activating and inhibitory signal from an inhibitory receptor LMIR3/CLM-1: LMIR3 augments lipopolysaccharide response through association with FcRγ in mast cells. J Immunol 183(2):925–936
Izawa K, Yamanishi Y, Maehara A, Takahashi M, Isobe M, Ito S, Kaitani A, Matsukawa T, Matsuoka T, Nakahara F, Oki T, Kiyonari H, Abe T, Okumura K, Kitamura T, Kitaura J (2012) The receptor LMIR3 negatively regulates mast cell activation and allergic responses by binding to extracellular ceramide. Immunity 37(5):827–839
Jackola DR, Pierson-Mullany LK, Liebeler CL, Blumenthal MN, Rosenberg A (2002) Variable binding affinities for allergen suggest a ‘selective competition’ among immunoglobulins in atopic and non-atopic humans. Mol Immunol 39(5–6):367–377
James LC, Roversi P, Tawfik DS (2003) Antibody multispecificity mediated by conformational diversity. Science 299(5611):1362–1367
Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, Walch E, Wirth T, O’Neill LA (2003) Bruton’s tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor κB activation by Toll-like receptor 4. J Biol Chem 278(28):26258–26264
Jimenez-Andrade GY, Ibarra-Sanchez A, Gonzalez D, Lamas M, Gonzalez-Espinosa C (2013) Immunoglobulin E induces VEGF production in mast cells and potentiates their pro-tumorigenic actions through a Fyn kinase-dependent mechanism. J Hematol Oncol 6:56
Jolly PS, Bektas M, Olivera A, Gonzalez-Espinosa C, Proia RL, Rivera J, Milstien S, Spiegel S (2004) Transactivation of sphingosine-1-phosphate receptors by FcεRI triggering is required for normal mast cell degranulation and chemotaxis. J Exp Med 199(7):959–970
Kalesnikoff J, Huber M, Lam V, Damen JE, Zhang J, Siraganian RP, Krystal G (2001) Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity 14(6):801–811
Kasakura K, Takahashi K, Aizawa T, Hosono A, Kaminogawa S (2009) A TLR2 ligand suppresses allergic inflammatory reactions by acting directly on mast cells. Int Arch Allergy Immunol 150(4):359–369
Kashiwakura J, Otani IM, Kawakami T (2011) Monomeric IgE and mast cell development, survival and function. Adv Exp Med Biol 716:29–46
Kashiwakura J, Okayama Y, Furue M, Kabashima K, Shimada S, Ra C, Siraganian RP, Kawakami Y, Kawakami T (2012) Most highly Cytokinergic IgEs have polyreactivity to autoantigens. Allergy Asthma Immunol Res 4(6):332–340
Katz HR, Vivier E, Castells MC, McCormick MJ, Chambers JM, Austen KF (1996) Mouse mast cell gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when colligated with the high-affinity Fc receptor for IgE. Proc Natl Acad Sci USA 93(20):10809–10814
Kawakami T, Galli SJ (2002) Regulation of mast-cell and basophil function and survival by IgE. Nat Rev Immunol 2(10):773–786
Kawakami Y, Kitaura J, Hata D, Yao L, Kawakami T (1999) Functions of Bruton’s tyrosine kinase in mast and B cells. J Leukoc Biol 65(3):286–290
Kennedy Norton S, Barnstein B, Brenzovich J, Bailey DP, Kashyap M, Speiran K, Ford J, Conrad D, Watowich S, Moralle MR, Kepley CL, Murray PJ, Ryan JJ (2008) IL-10 suppresses mast cell IgE receptor expression and signaling in vitro and in vivo. J Immunol 180(5):2848–2854
Kitaura J, Eto K, Kinoshita T, Kawakami Y, Leitges M, Lowell CA, Kawakami T (2005) Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases. J Immunol 174(8):4495–4504
Kitaura J, Song J, Tsai M, Asai K, Maeda-Yamamoto M, Mocsai A, Kawakami Y, Liu FT, Lowell CA, Barisas BG, Galli SJ, Kawakami T (2003) Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcεRI. Proc Natl Acad Sci USA 100(22):12911–12916
Komiya A, Nagase H, Okugawa S, Ota Y, Suzukawa M, Kawakami A, Sekiya T, Matsushima K, Ohta K, Hirai K, Yamamoto K, Yamaguchi M (2006) Expression and function of toll-like receptors in human basophils. Int Arch Allergy Immunol 140(Suppl 1):23–27
Kuo CH, Morohoshi K, Aye CC, Garoon RB, Collins A, Ono SJ (2012) The role of TRB3 in mast cells sensitized with monomeric IgE. Exp Mol Pathol 93(3):408–415
Laffargue M, Calvez R, Finan P, Trifilieff A, Barbier M, Altruda F, Hirsch E, Wymann MP (2002) Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell function. Immunity 16(3):441–451
Lee JH, Kim JW, Kim do K, Kim HS, Park HJ, Park DK, Kim AR, Kim B, Beaven MA, Park KL, Kim YM, Choi WS (2011) The Src family kinase Fgr is critical for activation of mast cells and IgE-mediated anaphylaxis in mice. J Immunol 187(4):1807–1815
Liao BC, Hou RC, Wang JS, Jeng KC (2006) Enhancement of the release of inflammatory mediators by substance P in rat basophilic leukemia RBL-2H3 cells. J Biomed Sci 13(5):613–619
Lienard H, Bruhns P, Malbec O, Fridman WH, Daeron M (1999) Signal regulatory proteins negatively regulate immunoreceptor-dependent cell activation. J Biol Chem 274(45):32493–32499
Lin S, Cicala C, Scharenberg AM, Kinet JP (1996) The FcεRIβ subunit functions as an amplifier of FceRIg-mediated cell activation signals. Cell 85(7):985–995
Liu Y, Furuta K, Teshima R, Shirata N, Sugimoto Y, Ichikawa A, Tanaka S (2005) Critical role of protein kinase C betaII in activation of mast cells by monomeric IgE. J Biol Chem 280(47):38976–38981
Madrenas J, Wange RL, Wang JL, Isakov N, Samelson LE, Germain RN (1995) Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science 267(5197):515–518
Marquardt DL, Parker CW, Sullivan TJ (1978) Potentiation of mast cell mediator release by adenosine. J Immunol 120(3):871–878
Matsuda K, Piliponsky AM, Iikura M, Nakae S, Wang EW, Dutta SM, Kawakami T, Tsai M, Galli SJ (2005) Monomeric IgE enhances human mast cell chemokine production: IL-4 augments and dexamethasone suppresses the response. J Allergy Clin Immunol 116(6):1357–1363
Matsushima H, Yamada N, Matsue H, Shimada S (2004) TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J Immunol 173(1):531–541
McCary C, Tancowny BP, Catalli A, Grammer LC, Harris KE, Schleimer RP, Kulka M (2010) Substance P downregulates expression of the high affinity IgE receptor (FcεRI) by human mast cells. J Neuroimmunol 220(1–2):17–24
McKeithan TW (1995) Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 92(11):5042–5046
Melendez AJ, Harnett MM, Pushparaj PN, Wong WS, Tay HK, McSharry CP, Harnett W (2007) Inhibition of Fc ε RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med 13(11):1375–1381
Metzger H (1977) The cellular receptor for IgE. In: Cuatrecasas P, Greaves MF (eds) Receptors and recognition. Chapman and Hall, London, pp 75–102
Metzger H (1978) The IgE-mast cell system as a paradigm for the study of antibody mechanisms. Immunol Rev 41:186–199
Metzger H (1983) The receptor on mast cells and related cells with high affinity for IgE. Contemp Top Mol Immunol 9:115–145
Metzger H (1992) Transmembrane signaling: the joy of aggregation. J Immunol 149(5):1477–1487
Meyaard L (2008) The inhibitory collagen receptor LAIR-1 (CD305). J Leukoc Biol 83(4):799–803
Miyazaki D, Nakamura T, Toda M, Cheung-Chau KW, Richardson RM, Ono SJ (2005) Macrophage inflammatory protein-1α as a costimulatory signal for mast cell-mediated immediate hypersensitivity reactions. J Clin Invest 115(2):434–442
Nadler MJ, Kinet JP (2002) Uncovering new complexities in mast cell signaling. Nat Immunol 3(8):707–708
Nakae S, Iikura M, Suto H, Akiba H, Umetsu DT, Dekruyff RH, Saito H, Galli SJ (2007) TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells. Blood 110(7):2565–2568
Nguyen M, Solle M, Audoly LP, Tilley SL, Stock JL, McNeish JD, Coffman TM, Dombrowicz D, Koller BH (2002) Receptors and signaling mechanisms required for prostaglandin E2-mediated regulation of mast cell degranulation and IL-6 production. J Immunol 169(8):4586–4593
Nishimoto H, Lee SW, Hong H, Potter KG, Maeda-Yamamoto M, Kinoshita T, Kawakami Y, Mittler RS, Kwon BS, Ware CF, Croft M, Kawakami T (2005) Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor. Blood 106(13):4241–4248
Novak N, Bieber T, Peng WM (2010) The immunoglobulin E-Toll-like receptor network. Int Arch Allergy Immunol 151(1):1–7
Ochi H, De Jesus NH, Hsieh FH, Austen KF, Boyce JA (2000) IL-4 and-5 prime human mast cells for different profiles of IgE-dependent cytokine production. Proc Natl Acad Sci USA 97(19):10509–10513
Okumura S, Kashiwakura J, Tomita H, Matsumoto K, Nakajima T, Saito H, Okayama Y (2003) Identification of specific gene expression profiles in human mast cells mediated by Toll-like receptor 4 and FcεRI. Blood 102(7):2547–2554
Olivera A (2008) Unraveling the complexities of sphingosine-1-phosphate function: the mast cell model. Prostaglandins Other Lipid Mediat 86(1–4):1–11
Olivera A, Mizugishi K, Tikhonova A, Ciaccia L, Odom S, Proia RL, Rivera J (2007) The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity 26(3):287–297
Olivera A, Rivera J (2011) An emerging role for the lipid mediator sphingosine-1-phosphate in mast cell effector function and allergic disease. Adv Exp Med Biol 716:123–142
On M, Billingsley JM, Jouvin MH, Kinet JP (2004) Molecular dissection of the FcRβ signaling amplifier. J Biol Chem 279(44):45782–45790
Ortega Soto E, Pecht I (1988) A monoclonal antibody that inhibits secretion from rat basophilic leukemia cells and binds to a novel membrane component. J Immunol 141(12):4324–4332
Oskeritzian CA, Price MM, Hait NC, Kapitonov D, Falanga YT, Morales JK, Ryan JJ, Milstien S, Spiegel S (2010) Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema. J Exp Med 207(3):465–474
Paar JM, Harris NT, Holowka D, Baird B (2002) Bivalent ligands with rigid double-stranded DNA spacers reveal structural constraints on signaling by Fc ε RI. J Immunol 169(2):856–864
Paolini R, Serra A, Kinet JP (1996) Persistence of tyrosine-phosphorylated FcεRI in deactivated cells. J Biol Chem 271(27):15987–15992
Parravicini V, Gadina M, Kovarova M, Odom S, Gonzalez-Espinosa C, Furumoto Y, Saitoh S, Samelson LE, O’Shea JJ, Rivera J (2002) Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol 3(8):741–748
Pasquier B, Launay P, Kanamaru Y, Moura IC, Pfirsch S, Ruffie C, Henin D, Benhamou M, Pretolani M, Blank U, Monteiro RC (2005) Identification of FcαRI as an inhibitory receptor that controls inflammation: dual role of FcRγ ITAM. Immunity 22(1):31–42
Pietrzak A, Wierzbicki M, Wiktorska M, Brzezinska-Blaszczyk E (2011) Surface TLR2 and TLR4 expression on mature rat mast cells can be affected by some bacterial components and proinflammatory cytokines. Mediators Inflamm 2011:427473
Pribluda VS, Pribluda C, Metzger H (1994) Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation. Proc Natl Acad Sci USA 91(23):11246–11550
Price KS, Friend DS, Mellor EA, De Jesus N, Watts GF, Boyce JA (2002) CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13. Am J Respir Cell Mol Biol 28(4):420–427
Price LS, Norman JC, Ridley AJ, Koffer A (1995) The small GTPases Rac and Rho as regulators of secretion in mast cells. Curr Biol 5(1):68–73
Pyenta PS, Schwille P, Webb WW, Holowka D, Baird B (2003) Lateral diffusion of membrane lipid-anchored probes before and after aggregation of cell surface IgE-receptors. J Phys Chem A 107:8310–8318
Qiao H, Andrade MV, Lisboa FA, Morgan K, Beaven MA (2006) FcεR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells. Blood 107(2):610–618
Ramkumar V, Stiles GL, Beaven MA, Ali H (1993) The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells. J Biol Chem 268(23):16887–16890
Rivera J, Fierro NA, Olivera A, Suzuki R (2008) New insights on mast cell activation via the high affinity receptor for IgE. Adv Immunol 98:85–120
Ryzhov S, Goldstein AE, Biaggioni I, Feoktistov I (2006) Cross-talk between G(s)- and G(q)-coupled pathways in regulation of interleukin-4 by A(2B) adenosine receptors in human mast cells. Mol Pharmacol 70(2):727–735
Saitoh S, Arudchandran R, Manetz TS, Zhang W, Sommers CL, Love PE, Rivera J, Samelson LE (2000) LAT is essential for FcεRI-mediated mast cell activation. Immunity 12(5):525–535
Schulman ES, Glaum MC, Post T, Wang Y, Raible DG, Mohanty J, Butterfield JH, Pelleg A (1999) ATP modulates anti-IgE-induced release of histamine from human lung mast cells. Am J Respir Cell Mol Biol 20(3):530–537
Selander C, Engblom C, Nilsson G, Scheynius A, Andersson CL (2009) TLR2/MyD88-dependent and -independent activation of mast cell IgE responses by the skin commensal yeast Malassezia sympodialis. J Immunol 182(7):4208–4216
Serra-Pages M, Olivera A, Torres R, Picado C, de Mora F, Rivera J (2012) E-prostanoid 2 receptors dampen mast cell degranulation via cAMP/PKA-mediated suppression of IgE-dependent signaling. J Leukoc Biol 92(6):1155–1165
Sibilano R, Frossi B, Suzuki R, D’Inca F, Gri G, Piconese S, Colombo MP, Rivera J, Pucillo CE (2012) Modulation of FcεRI-dependent mast cell response by OX40L via Fyn, PI3 K, and RhoA. J Allergy Clin Immunol 130(3):751–760e2
Sil D, Lee JB, Luo D, Holowka D, Baird B (2007) Trivalent ligands with rigid DNA spacers reveal structural requirements for IgE receptor signaling in RBL mast cells. ACS Chem Biol 2(10):674–684
Sloan-Lancaster J, Shaw AS, Rothbard JB, Allen PM (1994) Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Cell 79(5):913–922
Sonnenblick A, Levy C, Razin E (2005) Immunological trigger of mast cells by monomeric IgE: effect on microphthalmia transcription factor, STAT3 network of interactions. J Immunol 175(3):1450–1455
Suzuki R, Leach S, Dema B, Rivera J (2013) Characterization of a phospho-specific antibody to the Fcε receptor γ chain, reveals differences in the regulation of Syk and Akt phosphorylation. Antibodies 2:321–337
Suzuki R, Leach S, Liu W, Ralston E, Scheffel J, Zhang W, Lowell CA, Rivera J (2014) Molecular editing of cellular responses by the high-affinity receptor for IgE. Science 343(6174):1021–1025
Tashiro M, Kawakami Y, Abe R, Han W, Hata D, Sugie K, Yao L, Kawakami T (1997) Increased secretion of TNF-alpha by costimulation of mast cells via CD28 and Fc ε RI. J Immunol 158(5):2382–2389
Thomas JL, Holowka D, Baird B, Webb WW (1994) Large-scale co-aggregation of fluorescent lipid probes with cell surface proteins. J Cell Biol 125(4):795–802
Tkaczyk C, Horejsi V, Iwaki S, Draber P, Samelson LE, Satterthwaite AB, Nahm DH, Metcalfe DD, Gilfillan AM (2004) NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc ε RI aggregation. Blood 104(1):207–214
Toda M, Dawson M, Nakamura T, Munro PM, Richardson RM, Bailly M, Ono SJ (2004) Impact of engagement of FcεRI and CC chemokine receptor 1 on mast cell activation and motility. J Biol Chem 279(46):48443–48448
Tolar P, Hanna J, Krueger PD, Pierce SK (2009) The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens. Immunity 30(1):44–55
Torigoe C, Inman JK, Metzger H (1998) An unusual mechanism for ligand antagonism. Science 281(5376):568–572
Toru H, Pawankar R, Ra C, Yata J, Nakahata T (1998) Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking: enhanced IL-13 production by IL-4-primed human mast cells. J Allergy Clin Immunol 102(3):491–502
Uehara T, Blery M, Kang DW, Chen CC, Ho LH, Gartland GL, Liu FT, Vivier E, Cooper MD, Kubagawa H (2001) Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B. J Clin Invest 108(7):1041–1050
van der Merwe PA, Davis SJ (2003) Molecular interactions mediating T cell antigen recognition. Annu Rev Immunol 21:659–684
Varadaradjalou S, Feger F, Thieblemont N, Hamouda NB, Pleau JM, Dy M, Arock M (2003) Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. Eur J Immunol 33(4):899–906
Vonakis BM, Chen H, Haleem-Smith H, Metzger H (1997) The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE. J Biol Chem 272(38):24072–24080
Wang XS, Lau HY (2006) Prostaglandin E potentiates the immunologically stimulated histamine release from human peripheral blood-derived mast cells through EP1/EP3 receptors. Allergy 61(4):503–506
Weetall M, Holowka D, Baird B (1993) Heterologous desensitization of the high affinity receptor for IgE (FcεRI) on RBL cells. J Immunol 150(9):4072–4083
Wong MX, Roberts D, Bartley PA, Jackson DE (2002) Absence of platelet endothelial cell adhesion molecule-1 (CD31) leads to increased severity of local and systemic IgE-mediated anaphylaxis and modulation of mast cell activation. J Immunol 168(12):6455–6462
Woolhiser MR, Brockow K, Metcalfe DD (2004) Activation of human mast cells by aggregated IgG through FcγRI: additive effects of C3a. Clin Immunol 110(2):172–180
Woolhiser MR, Okayama Y, Gilfillan AM, Metcalfe DD (2001) IgG-dependent activation of human mast cells following up-regulation of FcγRI by IFN-γ. Eur J Immunol 31(11):3298–3307
Yamaguchi M, Lantz CS, Oettgen HC, Katona IM, Fleming T, Miyajima I, Kinet JP, Galli SJ (1997) IgE enhances mouse mast cell FcεRI expression in vitro and in vivo: evidence for a novel amplification mechanism in IgE-dependent reactions. J Exp Med 185(4):663–672
Yamasaki S, Ishikawa E, Kohno M, Saito T (2004) The quantity and duration of FcRgamma signals determine mast cell degranulation and survival. Blood 103(8):3093–3101
Yamashita T, Suzuki R, Backlund PS, Yamashita Y, Yergey AL, Rivera J (2008) Differential dephosphorylation of the FcRγ immunoreceptor tyrosine-based activation motif tyrosines with dissimilar potential for activating Syk. J Biol Chem 283(42):28584–28594
Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG, Hunt J, Hart P, Hughes JM, Perry MA, Alewood PF, Geczy CL (2007) S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol 119(1):106–114
Yokoi H, Choi OH, Hubbard W, Lee HS, Canning BJ, Lee HH, Ryu SD, von Gunten S, Bickel CA, Hudson SA, Macglashan DW, Jr, Bochner BS (2008) Inhibition of FcεRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement. J Allergy Clin Immunol 121(2):499–505e1
Yoshioka M, Fukuishi N, Iriguchi S, Ohsaki K, Yamanobe H, Inukai A, Kurihara D, Imajo N, Yasui Y, Matsui N, Tsujita T, Ishii A, Seya T, Takahama M, Akagi M (2007) Lipoteichoic acid downregulates FcεRI expression on human mast cells through Toll-like receptor 2. J Allergy Clin Immunol 120(2):452–461
Yotsumoto K, Okoshi Y, Shibuya K, Yamazaki S, Tahara-Hanaoka S, Honda S, Osawa M, Kuroiwa A, Matsuda Y, Tenen DG, Iwama A, Nakauchi H, Shibuya A (2003) Paired activating and inhibitory immunoglobulin-like receptors, MAIR-I and MAIR-II, regulate mast cell and macrophage activation. J Exp Med 198(2):223–233
Young RM, Holowka D, Baird B (2003) A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation. J Biol Chem 278(23):20746–20752
Young RM, Zheng X, Holowka D, Baird B (2005) Reconstitution of regulated phosphorylation of FcεRI by a lipid raft-excluded protein-tyrosine phosphatase. J Biol Chem 280(2):1230–1235
Zhang S, Cherwinski H, Sedgwick JD, Phillips JH (2004) Molecular mechanisms of CD200 inhibition of mast cell activation. J Immunol 173(11):6786–6793
Zorn CN, Keck S, Hendriks RW, Leitges M, Freudenberg MA, Huber M (2009) Bruton’s tyrosine kinase is dispensable for the toll-like receptor-mediated activation of mast cells. Cell Signal 21(1):79–86
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Suzuki, R., Scheffel, J., Rivera, J. (2015). New Insights on the Signaling and Function of the High-Affinity Receptor for IgE. In: Lafaille, J., Curotto de Lafaille, M. (eds) IgE Antibodies: Generation and Function. Current Topics in Microbiology and Immunology, vol 388. Springer, Cham. https://doi.org/10.1007/978-3-319-13725-4_4
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