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.
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.


CONCLUSIONS
According to our data, basophils are pure effector cells in the context of IgE-bound allergen and not involved in classical antigen presentation.
Wicklein
D
D
Research Center Borstel, Division of Molecular and Clinical Allergology, Parkallee, Borstel, Germany.
Stöcker
M
M
Klockenbring
T
T
Huhn
M
M
Wodrich
M
M
Haas
H
H
Becker
W-M
WM
Barth
S
S
Petersen
A
A
D036002:ADP Ribose Transferases / Q000032:analysis / Q000276:immunology; D000485:Allergens / Q000032:analysis / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001427:Bacterial Toxins / Q000032:analysis / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D005098:Exotoxins / Q000032:analysis / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D000922:Immunotoxins / Q000032:analysis / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D010940:Plant Proteins / Q000032:analysis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology; D012260:Ribonucleases / Q000032:analysis / Q000276:immunology; D057127:Single-Chain Antibodies; D037521:Virulence Factors / Q000032:analysis / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000485:Allergens; D001427:Bacterial Toxins; D005098:Exotoxins; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D000922:Immunotoxins; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012260:Ribonucleases; D057127:Single-Chain Antibodies; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C513566:425(scFv)-ETA'; C513565:P5-ETA'; C102306:Phl p Vb protein, Phleum pratense