Inhibition of IgE synthesis by anti-IgE: role in long-term inhibition of IgE synthesis by neonatally administered soluble IgE.

Haba, Seiji; Nisonoff, Alfred

doi:10.1073/pnas.87.9.3363

Cited by 34 publications

(17 citation statements)

References 13 publications

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“…However, few studies have examined the potential to deplete isotype-switched or memory B cells through BCR crosslinking. Two groups have found that perinatal immunization of mice with IgE, prior to the endogenous production of IgE, results in an IgE-specific antibody response that subsequently inhibits the generation of serum IgE in adult mice (29,30). However, immunization of adult mice is not effective due to the development of tolerance against IgE.…”

Section: Introductionmentioning

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.

100

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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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Section: Introductionmentioning

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.

100

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show abstract

“…We demonstrated that this is accompanied by profound decreases in the level of serum IgE and the number of IgEsecreting cells in the spleen (4,5 When IgE is inoculated in saline on the day of birth, it fails to elicit anti-IgE antibodies and renders mice tolerant to IgE inoculated on day 9 or 10 (that would otherwise have caused the synthesis of anti-IgE) (4). Tolerance to a challenge on day 9 can similarly be induced by inoculations of small (0.25 ,g) doses of IgE on days 3, 5, and 7; larger amounts of IgE (_5 ,ug) are immunogenic rather than tolerogenic when inoculated on these days (8,9).…”

Section: Introductionmentioning

confidence: 99%

“…KLH evidently provides the necessary T-cell help because adult mice do not respond to unconjugated IgE. Between the ages of 2 and 10 days, however, mice produce anti-IgE antibodies in response to unconjugated IgE administered in complete Freund's adjuvant (4) or in saline (5). The loss of responsiveness to unconjugated IgE correlates with the initial appearance of detectable IgE in serum at the approximate age of 2 wk (4, 5).…”

Section: Introductionmentioning

confidence: 99%

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IgE-secreting cells in the thymus: correlation with induction of tolerance to IgE.

Haba

Nisonoff

1992

Proc. Natl. Acad. Sci. U.S.A.

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“…Namely, anti-IgE antibodies that are useful for treatments, must not be anaphylactogenic and must be capable of neutralizing IgE in the sense that binding of IgE to effector cells of allergy is prevented. In vitro the inhibition of IgE synthesis has also been well documented [5, 6]. …”

Section: Introductionmentioning

confidence: 99%

Allergic Manifestations as the Results of a Conditional Autoimmune Response

Stadler

Miescher²,

Horn³

et al. 2001

Int Arch Allergy Immunol

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By means of repertoire cloning we have isolated human anti-IgE antibodies as well as human anti-FcΕRI antibodies. Whether the naturally occurring anti-IgE autoantibodies play a pathophysiological role may be disputed, but the beneficial role of recombinant anti-IgE antibodies as a therapeutic agent has been shown. On the other hand, the natural antibodies isolated from an antibody library of a nonallergic individual against the FcΕRI α-chain are anaphylactogenic, if FcΕRI was not occupied. Thus, anti-FcΕRI autoantibodies may be part of a conditional autoimmune reaction, leading to urticaria if local IgE is consumed, e.g. after an immediate reaction. Thus, anti-FcΕRI antibodies may represent an amplification arm of the late reaction. The normal occurrence of anti-IgE and anti-IgE receptor autoantibodies may suggest that it might also be feasible to induce such autoantibodies by vaccination. In a monkey model using a mimotope of human IgE it was possible to induce a beneficial anti- IgE autoimmune response. The actual epitope of the IgE molecule was then also molecularly reconstructed by generating recombinant anti-idiotypic antibodies. These antibodies also induced effectively an anti-IgE response in monkeys, suggesting that not only mimotopes but also anti-idiotypic antibodies may be used to generate an autoimmune response. Both of our projects suggest that active immunization may be a new form of immunomodulation for the treatment of allergic disease.

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Inhibition of IgE synthesis by anti-IgE: role in long-term inhibition of IgE synthesis by neonatally administered soluble IgE.

Cited by 34 publications

References 13 publications

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

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

IgE-secreting cells in the thymus: correlation with induction of tolerance to IgE.

Allergic Manifestations as the Results of a Conditional Autoimmune Response

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