Background: The dramatic increase of IgE-mediated allergic diseases in western countries demonstrates the urgent need for new therapeutic or prophylactic approaches. In mice, a prophylactic long-lasting allergen-specific suppression of IgE responsiveness is induced by maternal IgG antibodies to allergens like ovalbumin, phospholipase A(2) (bvPLA(2)) or ovomucoid. As neonatal application or maternally derived pathogen-reactive antibodies (idiotypes) as well as corresponding anti-idiotypes can induce anti-microbial protection, we probed the transgenerational IgE-suppressive mechanism with a syngeneic monoclonal anti-idiotypic antibody.
Methods: The monoclonal bee-venom-phospholipase A(2) (bvPLA(2))-reactive IgG antibody MS613 (idiotype) or the corresponding syngeneic anti-idiotype II/2-19 were injected during the first 2 days postpartum to the dams. Immunization of offspring with minute doses of IgE-inducing bvPLA(2) was started at an adult age of 3(1/2) months.
Results: The postnatal transfer of the anti-bvPLA(2) idiotype MS613 or the corresponding anti-idiotype II/2-19 induced long-lasting allergen-specific IgE suppression in a dose-dependent manner, while the IgG response to the allergen developed normally. Quantitatively, the anti-idiotype was more effective than idiotype. Molecular modeling of the idiotype-anti-idiotype complex and its comparison with the bvPLA(2) structure revealed that the anti-idiotype does not mimic bvPLA(2) epitopes and thus can not be regarded as an internal image antibody and, consequently, does not function as a surrogate antigen.
Conclusions: Idiotypic network reactivity is at least one major factor for induction of transgenerational IgE suppression by maternal IgG antibodies. If applicable to humans, these data suggest the possibility of a prophylactic and possibly therapeutic treatment of IgE-mediated allergic diseases with anti-idiotypic antibodies.