The Multifaceted B Cell Response in Allergen Immunotherapy

Abstract

While allergen immunotherapy (AIT) for IgE-mediated diseases holds curative potential, the considerable heterogeneity in clinical outcomes may relate to the complex mechanisms of tolerance. The regulation of humoral immunity by AIT contributes to the suppression of allergic responses. Recent findings have revealed novel roles for IgA and IgG antibodies in the induction of tolerance. These mechanisms synergize with their ability to block allergen-IgE binding and mediate inhibitory signalling of effector cells of the allergic response. In addition, the regulatory activity of B cells in AIT extends beyond IL-10 secretion and induction of IgG4. Here, we review the evolution of the B cell response during AIT with special emphasis on the novel protective mechanisms entailing humoral immunity.

Diverse Mechanisms of Allergen Specific Immunotherapy

“…On the other hand, perpetuated immunotherapy paves the way for reducing the levels of allergen-specific IgE which may promote long-term clinical tolerance [53]. Additionally, allergen-specific IgE levels in serum are prone to decrease over time, regardless of regular and increasing doses of allergen exposure [74] (Figure 2).…”

“…According to literature reports, an essential mechanism of immune tolerance to allergens is likely to involve an induction of IgG4, which captures the allergen before it reaches IgE. When IgG4 crosslinks with FcγRIIb, which is located on the surface of mast cells or basophils, this engagement prevents the activation of these cells [6,74,75]. Evidence of an IgG-FcɣRIIb link was demonstrated in foodallergic mice models [76].…”

“…Although there have been significant improvements in our current understanding on the mechanisms and basic contributions of humoral IgG, additional pathways need to be elucidated. The constricted perspective on allergen-specific IgG4 in AIT have omitted that other immunoglobulin subclasses in human allergic disease may contribute to the blocking and inhibitory response of IgG [74]. In vitro assays using IgG subclasses, other than IgG4, have shown the effector cell suppression via blocking IgE-allergen binding [75].…”

“…It has been suggested that IgG4 and IgA play a protective role after OIT was stopped [78]. Furthermore, salivary allergen-specific IgA was established as an effective biomarker in peanut sublingual AIT in humans, which is also correlated with the rating of tolerance posterior to AIT [74]. A recent study demonstrated that after 2 years of SCIT with HDM, Der p1-specific IgA increased in plasma relative to baseline levels.…”

“…Results indicate the durability of high-affinity antibodies also powerful in the context of neutralizing which has shown effective protection at low serum concentrations in the clinic. The de novo IgG4 response, which was induced during AIT, decreased after discontinuation of treatment [90], while the persistence of blocking antibodies was associated with clinical tolerance [74]. In brief, there is a need for further research to improve the efficacy of antibodies and potential roles as biomarkers.…”