Mechanisms of allergy
Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy

https://doi.org/10.1016/S0091-6749(03)02022-0Get rights and content

Abstract

Background

Among atopic individuals, levels of allergen-specific IgG antibodies have been inversely associated with the degree of allergen sensitization. Additionally, allergen-specific IgG antibodies are markedly increased by allergen injection immunotherapy. These observations have led to proposals that allergen-specific IgG antibodies might have protective properties in atopic individuals.

Objective

We hypothesized that after grass pollen immunotherapy, these antibodies disrupt IgE-dependent allergen processing by antigen-presenting cells.

Methods

We have developed a novel flow cytometric assay based on detection of allergen-IgE binding to the low-affinity IgE receptor on B cells to examine the blocking effects of sera collected from 18 patients who participated in a double-blind, controlled trial of grass pollen immunotherapy for 1 year.

Results

In all 10 patients who received active therapy, there was induction of activity that inhibited allergen-IgE binding to B cells (P = .02, vs placebo subjects), as well as subsequent allergen presentation to T cells. This activity copurified with IgG and was allergen specific, because sera taken from patients treated with grass pollen immunotherapy but who were also birch pollen sensitive did not inhibit IgE-birch pollen allergen binding to B cells.

Conclusion

We conclude that allergen-specific IgG antibodies induced by immunotherapy can disrupt formation of allergen-IgE complexes that bind to antigen-presenting cells and facilitate allergen presentation.

Section snippets

Study subjects

Forty patients with a history of severe, seasonal, allergic rhinitis that was not controlled by antiallergic drugs and a positive skin-test reaction (weal > 5 mm) to Phleum pratense (Phl p; Aquagen, ALK-Abelló, Hørsholm, Denmark) were randomized to treatment with IT or placebo injections for 1 year. From a randomly selected subgroup of 10 patients (7 men, 3 women; mean age, 36 years; range, 18 to 58) on active treatment and 8 patients (2 men, 6 women; mean age, 38 years; range, 26 to 51) on

Allergen-IgE binding to B cells: effects of allergen concentration, incubation time, CD23 blockade, and serum dilution

Allergen-dependent binding of IgE to the surfaces of EBV-transformed B cells was detected as early as 10 minutes after incubation with atopic IgE-containing serum (Phl p-specific IgE, 789 SU/ml) that had been preincubated with serial dilutions of grass pollen allergen (Phl p; Fig 1, A). The binding of serum-IgE was clearly dependent on the dilution of IgE-containing serum (Fig 1, B) and concentration of the allergen. Optimal binding was detectable at a relatively low allergen concentration (3.0

Discussion

In this study, we show that binding of IgE antibodies to CD23 on the surfaces of B cells is dramatically enhanced by the presence of low allergen concentrations, consistent with formation of “polymeric” allergen-IgE complexes that bind CD23 with greater avidity than “monomeric” IgE. This allergen-IgE binding to B cells was associated with enhanced stimulation of allergen-specific T-cell clones, suggesting that binding of complexes translates functionally into enhanced antigen processing and

Acknowledgements

We thank Dr Terry G. Merrett (Allergy Diagnostics Laboratory, Abingdon, UK) for measuring IgG in the serum samples and Dr Peter Adler-Würtzen (ALK-Abelló, Hørsholm, Denmark) for helpful comments on the manuscript.

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