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IgG subclasses determine pathways of anaphylaxis in mice

IgG subclasses determine pathways of anaphylaxis in mice
IgG subclasses determine pathways of anaphylaxis in mice
Background: Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (Fc?Rs). Mouse IgG2a and IgG2b bind activating Fc?RI, Fc?RIII, and Fc?RIV and inhibitory Fc?RIIB; mouse IgG1 binds only Fc?RIII and Fc?RIIB. Although these interactions are of strikingly different affinities, these 3 IgG subclasses have been shown to enable induction of systemic anaphylaxis.

Objective: We sought to determine which pathways control the induction of IgG1-, IgG2a-, and IgG2b-dependent passive systemic anaphylaxis.

Methods: Mice were sensitized with IgG1, IgG2a, or IgG2b anti-trinitrophenyl mAbs and challenged with trinitrophenyl-BSA intravenously to induce systemic anaphylaxis that was monitored by using rectal temperature. Anaphylaxis was evaluated in mice deficient for Fc?Rs injected with mediator antagonists or in which basophils, monocytes/macrophages, or neutrophils had been depleted. Fc?R expression was evaluated on these cells before and after anaphylaxis.

Results: Activating Fc?RIII is the receptor primarily responsible for all 3 models of anaphylaxis, and subsequent downregulation of this receptor was observed. These models differentially relied on histamine release and the contribution of mast cells, basophils, macrophages, and neutrophils. Strikingly, basophil contribution and histamine predominance in mice with IgG1- and IgG2b-induced anaphylaxis correlated with the ability of inhibitory Fc?RIIB to negatively regulate these models of anaphylaxis.

Conclusion: We propose that the differential expression of inhibitory Fc?RIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass–dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo.
0091-6749
1-19
Beutier, H.
cd24408b-3941-4879-a305-d11db60b6a86
Gillis, C.M.
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Iannascoli, B.
000a3b7e-d019-4fab-ada3-485875d2643c
Godon, O.
a87cf1dc-f625-4ed3-87c5-ccb831a1028d
England, P.
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Sibilano, R.
fc6dd87c-55a8-4e5a-8d9c-9f7d07d89f2e
Reber, L.L.
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Galli, S.J.
63329251-d4d7-4d90-9112-888a8bea4db6
Cragg, M.S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Van Rooijen, N.
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Nancardi, D.A.
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Bruhns, P.
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Jonnson, F.
eef27666-b4d5-4ec9-aa31-ec1e3e1c924f
Beutier, H.
cd24408b-3941-4879-a305-d11db60b6a86
Gillis, C.M.
2c954eee-2434-4384-81c0-2afd33274fd4
Iannascoli, B.
000a3b7e-d019-4fab-ada3-485875d2643c
Godon, O.
a87cf1dc-f625-4ed3-87c5-ccb831a1028d
England, P.
031fee23-c4c9-4951-bf17-c0a6b464bcec
Sibilano, R.
fc6dd87c-55a8-4e5a-8d9c-9f7d07d89f2e
Reber, L.L.
c580ca89-d357-4f74-8f64-3c885b6bc103
Galli, S.J.
63329251-d4d7-4d90-9112-888a8bea4db6
Cragg, M.S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Van Rooijen, N.
82584b63-9bea-4258-a425-60cbb9d54483
Nancardi, D.A.
59665912-d71c-4aee-8aed-d01313c4da35
Bruhns, P.
be14ed57-000f-42de-8e80-5226355143f5
Jonnson, F.
eef27666-b4d5-4ec9-aa31-ec1e3e1c924f

Beutier, H., Gillis, C.M., Iannascoli, B., Godon, O., England, P., Sibilano, R., Reber, L.L., Galli, S.J., Cragg, M.S., Van Rooijen, N., Nancardi, D.A., Bruhns, P. and Jonnson, F. (2016) IgG subclasses determine pathways of anaphylaxis in mice. Journal of Allergy and Clinical Immunology, 1-19. (doi:10.1016/j.jaci.2016.03.028). (PMID:27246523)

Record type: Article

Abstract

Background: Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (Fc?Rs). Mouse IgG2a and IgG2b bind activating Fc?RI, Fc?RIII, and Fc?RIV and inhibitory Fc?RIIB; mouse IgG1 binds only Fc?RIII and Fc?RIIB. Although these interactions are of strikingly different affinities, these 3 IgG subclasses have been shown to enable induction of systemic anaphylaxis.

Objective: We sought to determine which pathways control the induction of IgG1-, IgG2a-, and IgG2b-dependent passive systemic anaphylaxis.

Methods: Mice were sensitized with IgG1, IgG2a, or IgG2b anti-trinitrophenyl mAbs and challenged with trinitrophenyl-BSA intravenously to induce systemic anaphylaxis that was monitored by using rectal temperature. Anaphylaxis was evaluated in mice deficient for Fc?Rs injected with mediator antagonists or in which basophils, monocytes/macrophages, or neutrophils had been depleted. Fc?R expression was evaluated on these cells before and after anaphylaxis.

Results: Activating Fc?RIII is the receptor primarily responsible for all 3 models of anaphylaxis, and subsequent downregulation of this receptor was observed. These models differentially relied on histamine release and the contribution of mast cells, basophils, macrophages, and neutrophils. Strikingly, basophil contribution and histamine predominance in mice with IgG1- and IgG2b-induced anaphylaxis correlated with the ability of inhibitory Fc?RIIB to negatively regulate these models of anaphylaxis.

Conclusion: We propose that the differential expression of inhibitory Fc?RIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass–dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo.

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Accepted/In Press date: 3 March 2016
e-pub ahead of print date: 26 April 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 396323
URI: http://eprints.soton.ac.uk/id/eprint/396323
ISSN: 0091-6749
PURE UUID: c5c78143-b83b-4663-bcc6-156563551111
ORCID for M.S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 08 Jun 2016 09:16
Last modified: 17 Dec 2019 06:47

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Contributors

Author: H. Beutier
Author: C.M. Gillis
Author: B. Iannascoli
Author: O. Godon
Author: P. England
Author: R. Sibilano
Author: L.L. Reber
Author: S.J. Galli
Author: M.S. Cragg ORCID iD
Author: N. Van Rooijen
Author: D.A. Nancardi
Author: P. Bruhns
Author: F. Jonnson

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