KEYWORDS

Allergy, affinity, antibody, IgE, IgG.1 Introduction
The discovery of IgE-mediated allergic disease as an indication of hay-fever, or allergic rhinitis, was first described in 1819 by John Bostock, a medical doctor who himself suffered from hay fever1. He called the disease catarrhus aestivus, summer catarrh, as it was invariably absent in winter time. Catarrhus aestivus was a rare disease in the early nineteenth century, and after reporting his own case, it took him more than nine years to identify another 28 cases for publishing a second article 2. At the beginning of the 20th century, allergens were considered being toxins 3. Only with the discovery of IgE antibodies 4,5, it became evident that allergen-specific antibodies are the reason for the aberrant response of the body against pollen.
In clinical practice, there are several possibilities to avoid the activity of IgE and many pharmaceutical interventions aim to prevent IgE production and/or make the immune system more tolerant to allergens by inducing a shift in Th cell responses from Th2 to Th1 or regulatory T cells 6,7; more recently, the concept of mAbs targeting and blocking IgE directly has been introduced8. Alternatively, it may be possible to block the action of IgE indirecty by induction of allergen-specific IgG through passive 9 or active vaccination10,11. This approach is supported by the clinical observation that successful specific immunotherapy may correlate with an increase of the IgG/IgE ratio, and more recently, that polyclonal and monoclonal allergen specific IgG antibodies were able to curb allergic immune responses both in mice and humans as a form of passive vaccination 12-14. Hence, it seems reasonable to conclude that the overarching goal of immunotherapy should be the induction of allergen-specific IgG antibodies.
This raises the question of antibody specificity and quality. Which are the key parameters driving or inhibiting allergic responses? As outlined below, the answer is complex and different for IgE mediated activation by allergen versus IgG mediated neutralization of allergen versus FcγRIIb-mediated inhibition of allergic responses (Figure 1). The same is true for antibody specificity, as rules for IgE-mediated activation versus IgG-mediated blockade or FcγRIIb-mediated inhibition are fundamentally different. Perhaps unexpectedly, the role of IgG subclasses plays only a minor role in inhibiting the allergic response.