Reactivity of Mast-Cell-Bound IgE Idiotypes with Anti-Idiotypic Antibody: Mediator Release or Inhibition of Antigen-Induced Mediator Release?

Abstract

When anti-idiotypic antibodies specific for idiotopes on IgE antibodies react with mast-dell-bound IgE antibody, the reaction may be expected to lead either to mediator release or to inhibition of allergen-induced release. This study was carried out to determine which would occur. Anti-idiotype antiserum (anti-Ids) was raised in syngeneic mice by immunisation with affinity-purified DNP-specific mouse monoclonal IgE. Sera from these immunised mice and from a similarly immunised rabbit inhibited the binding of the monoclonal IgE to radio-iodinated dinitrophenylated (DNP) ovalbumin, whereas a high concentration of affinity-purified rabbit antimouse ε-chain-specific antibody was unable to inhibit even though it was shown to bind to the monoclonal IgE. The mouse anti-Ids did not give a positive passive cutaneous anaphylactic reaction in rats sensitised with high-titre grass-pollen-specific IgE-containing antiserum, whereas it gave a positive result in rats sensitised with the DNP-specific monoclonal IgE. Rabbit antimonoclonal antiserum and rabbit anti-ε-chain antibody both gave positive results in these two assays. The results indicated that anti-idiotypic antibodies specific for idiotopes on IgE antibody can react and release mediators from IgE-sensitised mast cells. The significance of this in view of the increased levels of anti-idiotypes that can occur during immunotherapy is discussed.

Anti-Ids in Allergy: Timeliness of a Classic Concept

“…4C). Furthermore, successful immunotherapy was considered to rely on continuous anti-id targeting of the mast cells rendering internalization and, therefore, depletion of cell bound specific IgE 28…”

Human auto‐anti‐idiotypic antibodies to mite‐specific IgE can degranulate human basophils in vitro

“…Do anti-Id antibodies have a role in triggering histamine release from basophils and mastocytes or do tliey have the capacity to block the allergen-induced histamine release, besides of course iheir potential to regulate the production of antibodies carrying the corresponding idiotypes? This question has already been debated [17]. The protection ofthe allergen binding site by paratope-speclfic anti-Ids would be beneficial if IgE is linked to anti-Ids without extensive basophil degranulation and indeed the above-mentioned reasons make anti-Id antibodies good candidates as weak degranulators.…”

“…Of particular interest in this regard is the capacity of anti-Ids to specifically recognize Ids carried by IgE antibodies [16]. Interaction with IgE antibodies located at the surface of a basophil or mastocyte could indeed result in two types of effects: crosslinkiniz of IgE molecules and degranulation of the cell, or inhibition of allergen-dependent degranuiation [17], Deciding which of these two phenomena would predominate is of obvious importance for our understanding of how anti-Ids act physiologically, but also for the design of therapies whose aim would be to increase the production of anti-Ids [IS], Anti-!ds raised in animals can recognize Ids carried by surface-bound IgE, Thus, mouse anti-Ids can induce a passive cutaneous anaphylactic response and release of mediators from IgE-sensiti/ed rat mast cells [17], Rabbit polyclonal and murine monoclonal anti-Ids have been shown to interact with human IgE on the hasophil surface, resulting in histamine release [19.20]. However, whether human anti-Ids could interact with human IgE on basophils has never been demonstrated.…”

Heterogeneity in the IgE Binding to a Peptide Derived from the House Dust Mite Allergen <i>Der </i><i>p</i> II Indicates that the IgE Response Is Highly Polyclonal

“…Two possible mecha nisms haven been suggested to account for the desensitiz ing effect of auto-anti-idiotype antibodies. As anti-idio type antibodies mimic the allergen they were believed to inhibit binding of allergen to mast cell bound specific IgE without being able to induce mast cell degranulation, how ever several groups found that anti-idiotype antibodies can induce histamine release from mast cells [7,8], Anoth er mechanism explains the desensitizing effect of anti-idi otype antibodies by depletion of cell-bound IgE by contin uous triggering of the mast cells by subsymptomatic doses of these antibodies. This type of immunotherapy is more likely to be successful!…”