Allergen-Specific Antibodies Regulate Secondary Allergen-Specific Immune Responses

Abstract

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically pre-disposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergen-specific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses.

Relationship between serum inhibitory activity for IgE and efficacy of Artemisia pollen subcutaneous immunotherapy for allergic rhinitis: a preliminary self-controlled study

“…Further, its bispecific activity makes it possible that allergen sIgG4 could oligomerize allergen molecules. Consistently, Eckl-Dorna et al mentioned that allergen specific IgG could further oligomerize IgE-allergen complexes by supercrosslinking, leading to the crosslinking of IgE + BCRs (B cell receptors) and thus activation of effective T cells, as well as the mediator release of mast cells (MCs) [30]. So the sIgGs, especially sIgG4s, can not only act as inhibitory antibodies to serve as protective factor, but exacerbate the allergic inflammation.…”

“…Especially, T cell activation mediates late phase reactions by increasing the levels of Th2 cytokines and then recruiting eosinophil and causing tissue damage and remodeling [31]. Receptor-mediated internalization of allergen-IgE complexes via high (FcεRI) affinity and low (CD23) affinity receptors for IgE by APCs-a process called facilitated antigen presentation (FAP)-has been shown to stimulate allergen-specific T cell proliferation more efficiently, in particular at low concentrations of allergen as they occur in vivo in allergic patients, and CD23-mediated FAP by non-cognate B cells is an important mechanism in driving AR [30]. The process FAP is tested in ELIFAB and it was indeed inhibited after SCIT in this study and other former reports [15,16,32], but there are many other ways to activate T cell and further induce T cell proliferation and cytokine production.…”

“…The process FAP is tested in ELIFAB and it was indeed inhibited after SCIT in this study and other former reports [15,16,32], but there are many other ways to activate T cell and further induce T cell proliferation and cytokine production. T cells can be activated by internalization of allergen via fluid phase endocytosis by APCs [30]. Further, it's the degranulation of mast cells and basophils that leads to allergic inflammation and symptoms, like nasal congestion, itchy nose and ocular pruritus directly, but activity of mast cells and basophils is influenced by many factors besides activated T cells.…”

Diverse Mechanisms of Allergen Specific Immunotherapy

“…Evidence of an IgG-FcɣRIIb link was demonstrated in foodallergic mice models [76]. Conclusion of IgG4 related reports suggests that AIT-induced allergen specific IgGs may block mast cell degranulation [68] and downregulate IL-4 secretion thus conducts Tregs and Th2 balance in allergic individuals [4] (Figure 2).…”

“…In addition to basophils and mast cells, many other cell types can contribute to early immunotherapy responses. APCs can bind and internalize allergen-IgE immune complexes and therefore enhance allergen-specific T cell activation [68]. Recent studies described the main role of Tregs and classical/conventional dendritic cells (cDCs) related with oral tolerance, which requires the CCR7 dependent fundamental migration of cDCs from the lamina propria (LP) to draining mesenchymal lymph nodes (MesLNs) [69,70].…”