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

• Published in: Clinical and experimental allergy Vol. 36; no. 4; pp. 531 - 542
• Main Authors: Wicklein, D., Stöcker, M., Klockenbring, T., Huhn, M., Wodrich, M., Haas, H., Becker, W.-M., Barth, S., Petersen, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006; Blackwell; Wiley Subscription Services, Inc
• Subjects: ADP Ribose Transferases - analysis; ADP Ribose Transferases - immunology; allergen; allergen toxin; Allergens - analysis; Allergens - immunology; Allergic diseases; Animals; B-Lymphocytes - immunology; Bacterial Toxins - analysis; Bacterial Toxins - immunology; basophils; Basophils - immunology; Biological and medical sciences; Cell Line; Cytotoxicity Tests, Immunologic - methods; Exotoxins - analysis; Exotoxins - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; hybridoma cells; Hybridomas - immunology; Immunoglobulin E - immunology; Immunoglobulin G - immunology; Immunopathology; Immunotoxins - analysis; Immunotoxins - immunology; Leukocytes, Mononuclear - immunology; Medical sciences; Mice; Models, Animal; Plant Proteins - analysis; Plant Proteins - immunology; Pseudomonas; Pseudomonas aeruginosa Exotoxin A; Recombinant Fusion Proteins - analysis; Recombinant Fusion Proteins - immunology; Recombinant Proteins - immunology; Respiratory Hypersensitivity - immunology; Ribonucleases - analysis; Ribonucleases - immunology; Single-Chain Antibodies; Virulence Factors - analysis; Virulence Factors - immunology; Human; Immunopathology; Allergy; IgE; Granulocyte; hybridoma cells; Hybridoma; B-Lymphocyte; allergen toxin; basophils; Biological activity; Basophil; Toxin; Immunology; Internalization; Allergen
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02461.x

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.