Targeting the extracellular membrane-proximal domain of membrane-bound IgE by passive immunization blocks IgE synthesis in vivo.
The classical allergic reaction starts seconds or minutes after Ag contact and is committed by Abs produced by a special subset of B lymphocytes. These Abs belong to the IgE subclass and are responsible for Type I hyperreactivity reactions. Treatment of allergic diseases with humanized anti-IgE Abs leads primarily to a decrease of serum IgE levels. As a consequence, the number of high-affinity IgE receptors on mast cells and basophils decreases, leading to a lower excitability of the effector cells. The biological mechanism behind anti-IgE therapy remains partly speculative; however, it is likely that these Abs also interact with membrane IgE (mIgE) on B cells and possibly interfere with IgE production. In the present work, we raised a mouse mAb directed exclusively against the extracellular membrane-proximal domain of mIgE. The interaction between the monoclonal anti-mIgE Ab and mIgE induces receptor-mediated apoptosis in vitro. Passive immunization experiments lead to a block of newly synthesized specific IgEs during a parallel application of recombinant Bet v1a, the major birch pollen allergen. The decrease of allergen-specific serum IgE might be related to tolerance-inducing mechanisms stopping mIgE-displaying B cells in their proliferation and differentiation.
Feichtner
Stefan
S
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Inführ
Daniela
D
Achatz-Straussberger
Gertrude
G
Schmid
Doris
D
Karnowski
Alexander
A
Lamers
Marinus
M
Rhyner
Claudio
C
Crameri
Reto
R
Achatz
Gernot
G
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001491:Basophils / Q000276:immunology*; D029662:Betula / Q000276:immunology; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000276:immunology; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism
D000485:Allergens; D000911:Antibodies, Monoclonal; D017455:Receptors, IgE; D007073:Immunoglobulin E