Tracing IgE-Producing Cells in Allergic Patients

Abstract

Immunoglobulin E (IgE) is the key immunoglobulin in the pathogenesis of IgE associated allergic diseases affecting 30% of the world population. Recent data suggest that allergen-specific IgE levels in serum of allergic patients are sustained by two different mechanisms: inducible IgE production through allergen exposure, and continuous IgE production occurring even in the absence of allergen stimulus that maintains IgE levels. This assumption is supported by two observations. First, allergen exposure induces transient increases of systemic IgE production. Second, reduction in IgE levels upon depletion of IgE from the blood of allergic patients using immunoapheresis is only temporary and IgE levels quickly return to pre-treatment levels even in the absence of allergen exposure. Though IgE production has been observed in the peripheral blood and locally in various human tissues (e.g., nose, lung, spleen, bone marrow), the origin and main sites of IgE production in humans remain unknown. Furthermore, IgE-producing cells in humans have yet to be fully characterized. Capturing IgE-producing cells is challenging not only because current staining technologies are inadequate, but also because the cells are rare, they are difficult to discriminate from cells bearing IgE bound to IgE-receptors, and plasma cells express little IgE on their surface. However, due to the central role in mediating both the early and late phases of allergy, free IgE, IgE-bearing effector cells and IgE-producing cells are important therapeutic targets. Here, we discuss current knowledge and unanswered questions regarding IgE production in allergic patients as well as possible therapeutic approaches targeting IgE.

Nanobodies—Useful Tools for Allergy Treatment?

“…Nevertheless, all mentioned technologies are also reported to have some limitations. While the hybridoma technology and EBV transformation are generally unsuitable for a comprehensive screening of large antibody repertoires because of their inefficient fusion and transformation events, the single B cell sorting was long hampered by inadequate staining technologies to clearly identify allergen-specific antibody producing cells (32,39). The main drawback of combinatorial libraries is that they usually rely on random combination and thus most likely unnatural VH and VL antibody pairings.…”

“…Amongst them the choice for the perfect source to gain DNA coding for antibodies and the applied technology to generate allergen-specific antibodies are two of the most critical ones. Regarding the DNA source both animals, mainly mice, and humans served as blood, spleen, tonsils and even bone marrow donors in the last decades to isolate B cells or plasma cells and thus DNA coding for antibodies ( 30 – 32 ). For the proof of principle, murine IgG antibodies overlapping with human IgE binding sites are valuable tools to investigate the effects to inhibit IgE epitope recognition on allergens and consequently to contribute to the design of hypoallergenic derivatives suitable for AIT ( 33 ).…”

Preventive Allergen-Specific Vaccination Against Allergy: Mission Possible?

“…Whether an individual develops allergen-specific IgE antibodies or not depends on a large variety of host and environmental factors including genetic factors predisposing for IgE production as well as allergen exposure and adjuvant factors to just name a few ( 9 ). IgE antibodies belong to the least abundant class of immunoglobulins in humans ( 10 ). However, IgE can bind to the high affinity receptor for IgE (FcεRI) on mast cells and basophils and to the low affinity IgE receptor (CD23) on B cells and antigen presenting cells.…”

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

“…In the context of allergy, activation of allergic-specific T cells is the key step to induce allergic symptom. 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].…”