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In contrast to specific B cells, human basophils are unaffected by the toxic activity of an allergen toxin due to lack of internalization of immunoglobulin E-bound allergen

Authors


  • This work was supported by the Deutsche Forschungsgemeinschaft, Grant DFG PE-491/6 and BA-1772/4.

Correspondence:
Arnd Petersen, Research Center Borstel, Division of Molecular and Clinical Allergology, Parkallee 1-40, 23845 Borstel, Germany.
E-mail: apetersen@fz-borstel.de

Summary

Background Specific immunotherapy is the only curative therapy for type I allergies and the alarming increase in allergy prevalence emphasizes the need for additional/alternative strategies for curative treatment. Allergen toxins (AT), fusion products of an allergen with an apoptosis inducing cytotoxin, are a new kind of immunotoxin.

Objective AT should allow allergen-specific targeting and elimination of allergy-relevant cells, with B cells being the primary target. An important question is the fate of the effector cells, e.g. mast cells and basophils, which carry allergen-specific IgE: the immunotoxin might even prove to be harmful.

Methods We established a reliable in vitro B cell model (using two mouse hybridoma cell lines) for testing specificity and toxicity of P5-ETA′, a fusion protein of the major timothy grass pollen allergen Phl p 5b and truncated Pseudomonas Exotoxin A. In a second step, we investigated the impact of the AT on human basophils.

Results P5-ETA′ reliably eliminated Phl p 5-specific cells in the in vitro B cell model, leaving unspecific B cells unharmed. Human basophils of grass pollen allergic donors specifically bound P5-ETA′, released IL-4 and up-regulated the activation marker CD203c, but were not subject to the toxic effect because of lack of internalization of IgE-bound allergen.

Conclusion According to our data, basophils are pure effector cells in the context of IgE-bound allergen and not involved in classical antigen presentation.

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