Establishment of a Memory in vitro Murine IgE Response to Benzylpenicillin and its Resistance to Suppression by Anti-lL-4 Antibody

Heusser, C H; Wagner, Kathrin; Brinkmann, Volker; Severinson, Eva; Blaser, Kurt

doi:10.1159/000235075

Cited by 18 publications

(12 citation statements)

References 7 publications

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“…We have reported that anti-TNP IgE re sponse can be induced by in vitro restimulation of murine SC that had been primed with TNP-KLH twice [17][18][19]. It has been shown by Heusser et al [23] that memory antibenzylpenicilloyl (BPO) IgE response was observed in BPO-KLH-primcd murine SC culture. For analyzing the role of Th cells and their cytokines, it is useful to induce antigen-specific antibody responses using Th clones.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, antigen-specific memory IgE responses to BPO-KLH [23] and KLH [25] have been reported to be refrac tory to the blockade by anti-IL4. Stevens et al [26] have shown that anti-TNP IgGl response induced in the cocul ture of murine B cells with KLH-specific Th2 clone in the presence of TNP-KLH was suppressed only partially by anti-IL4.…”

Section: Discussionmentioning

confidence: 99%

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Antigen-Specific But Not Polyclonal IgE Response in Murine B Cells Cocultured with Th2 Clone is Refractory to Suppression by IL4-Depletion

Haruna

Hara²,

Ohmori³

1993

Int Arch Allergy Immunol

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We established culture conditions allowing the induction of antitrinitrophenyl (TNP) IgE response by the coculture of unprimed C3H B cells with conalbumin (CA)-specific type 2 helper T cell clone, D10.G4.1 in the presence of TNP-CA With the help of this culture system, the role of Th2 cells and interleukin 4 (IL4) derived from them in the induction of antigen-specific IgE response was analyzed. A maximum level of anti-TNP IgE was secreted at 0.5-1 μg/ml TNP-CA. When the antigen was increased to 100 μg/ml, anti-TNP IgE production was abolished, while antigen-nonspecific (polyclonal) IgE was produced concomitantly. Anti-TNP IgE synthesis was not significantly suppressed in the presence of monoclonal anti-IL4 (11B11), nor was the response further enhanced by the addition of recombinant IL4. In contrast, polyclonal IgE response was abolished by 11B11. In order to deplete endogenous IL4 more strictly, we employed an antisense DNA for IL4 mRNA that can effectively inhibit IL4 production from D10 cells. Even in the presence of both 11B11 and the antisense DNA, it was found that anti-TNP IgE response was not suppressed significantly. These results suggest that antigen-specific IgE response induced in B cells cocultured with established Th2 cells does not depend on IL4 in contrast to polyclonal IgE response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antigen-Specific But Not Polyclonal IgE Response in Murine B Cells Cocultured with Th2 Clone is Refractory to Suppression by IL4-Depletion

Haruna

Hara²,

Ohmori³

1993

Int Arch Allergy Immunol

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“…The regulation and existence of IgE memory B cells is controversial and poorly understood (50)(51)(52)(53)(54)(55)(56). It has been suggested that a significant fraction of IgE memory resides in the IgG1 compartment, with generation of a memory IgE response resulting from sequential switching of IgG1 memory B cells to the IgE B cell lineage (50,54,(57)(58)(59)(60)(61)(62)(63)(64).…”

Section: Figurementioning

confidence: 99%

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Brightbill¹,

Jeet²,

Lin³

et al. 2010

J. Clin. Invest.

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IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is in general an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, we have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1′ domain, and using genetically modified mice that contain the human M1′ domain inserted into the mouse IgE locus, we demonstrated that M1′-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1′-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, we generated a humanized M1′-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apoptosis-inducing M1′-specific antibodies may be a novel treatment for asthma and allergy.

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“…Spleen cells derived from mice which were immunized with benzyl-penicillinoyl (BPO) conjugated KLH 3 months previously, re sponded in culture to the antigen with IgE anti-BPO antibody formation [26]. This IgE response could not be inhibited by anti-I L-4 antibodies.…”

Section: Il-4 Independent Ongoing and Secondary Ige Responsesmentioning

confidence: 99%

“…Although IgE determina tions were performed by an ELISA which is not af fected by the systemically used anti-IgE antibodies, the observed low serum IgE titers may just reflect im mune-complex-mediated clearance of serum IgE. In order to determine the effect of nonanaphylactic antiIgE antibodies on the new formation of IgE, the IgE production was also analyzed on the single antibody forming cell (AFC) level by an antigen-specific ELISA-spot assay [26]. Mice which received anti-IgE antibodies during booster injections contained less than 50% BPO-specific IgE AFC in the spleen, if com pared to control animals, whereas IgGl AFC were not affected.…”

Section: Selective Inhibition Of Ige Formation By Nonanaphylactic Antmentioning

confidence: 99%

New Concepts of IgE Regulation

Heusser

Bews

Brinkmann

et al. 1991

Int Arch Allergy Immunol

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B cell switch to IgE expression is mediated by IL-4 and is regarded as a T helper cell-related phenomenon. In this overview we describe that IgE switch can also be induced by mast cell/basophil like cells (from splenic non-B, non-T cells), activated by IgE receptor cross-linking and/or IL-3 which results in IL-4 production by these cells. Furthermore, activated mast cells produce their own growth factors, IL-3 and GM-CSF. Thus, activation of mast cells can provoke an ongoing local allergic reaction as long as antigen confrontation is maintained, a process which is sustained by further IgE production as well as renewal of mast cells. It is furthermore demonstrated that in certain established immune situations the IgE response may become independent of IL-4, namely in the spontaneous in vitro IgE expression of cells from atopic individuals as well as in an in vitro antigen-induced secondary IgE response of spleen cells derived from previously immunized mice. Thus, IgE-switched B cells may persist in vivo and may represent a pool of potentially IgE-producing cells. Finally, a selective inhibiton of the IgE response is described in vitro and in vivo by the use of so-called non-anaphylactic monoclonal anti-IgE antibodies. Such antibodies bind to surface IgE⁺ B cells, but not to IgE-sensitized mast cells, and thereby inhibit IgE responses. Nonanaphylactic antibodies blocked the binding of allergen-specific IgE to mast cells by competing with the Fc_ε on these cells. As a consequence they do not induce but rather prevent allergen-induced mediator release by mast cells. It is believed that corresponding antibodies to human IgE used in the chimeric (humanized) form will represent an attractive possibility to inhibit and/or eliminate IgE-switched B cells in vivo. This may lead to an efficient and isotype-specific suppression of human IgE responses.

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Establishment of a Memory in vitro Murine IgE Response to Benzylpenicillin and its Resistance to Suppression by Anti-lL-4 Antibody

Cited by 18 publications

References 7 publications

Antigen-Specific But Not Polyclonal IgE Response in Murine B Cells Cocultured with Th2 Clone is Refractory to Suppression by IL4-Depletion

Antigen-Specific But Not Polyclonal IgE Response in Murine B Cells Cocultured with Th2 Clone is Refractory to Suppression by IL4-Depletion

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

New Concepts of IgE Regulation

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