Reversal of the adult IgE high responder phenotype in mice by maternally transferred allergen-specific monoclonal IgG antibodies during a sensitive period in early ontogeny.
IgE is an important trigger in allergy and asthma, diseases whose development is suggested to depend on an initial sensitization in early life. While induction of murine IgE responses requires both a genetically based IgE high responder phenotype and defined experimental conditions, maternally transferred IgG can override these prerequisites and suppress IgE formation in an allergen-specific manner. Here, we show that maternally transferred monoclonal IgG, irrespective of their subclass and recognized epitopes, induce IgE unresponsiveness, which is effective for parenteral immunization with bee venom phospholipase A2 as well as for airway-immunization with nebulized ovomucoid-containing ovalbumin. This IgE suppression is detectable in the offspring during the first 4 months of life, but not thereafter and not in the dams. However, when the initial immunization at an age of 3 or 4 months was followed by further application of both allergens via their respective routes, IgE suppression persisted up to an age of more than one year. If applicable to man, these findings may allow the development of a new strategy for the prevention of allergy and asthma by maternally transferred or neonatally injected allergen-specific mAb in combination with natural or prophylactic exposure to the respective allergens during early childhood.
Lange
Hans
H
Biochemical Institute, Medical Faculty, Christian-Albrechts-Universität at Kiel, Germany.
Kiesch
Berit
B
Linden
Isabelle
I
Otto
Marcus
M
Thierse
Hermann J
HJ
Shaw
Lee
L
Maehnss
Karen
K
Hansen
Hinrich
H
Lemke
Hilmar
H
D000367:Age Factors; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001514:Bee Venoms / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007112:Immunity, Maternally-Acquired; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010059:Ovomucin / Q000276:immunology; D010741:Phospholipases A / Q000276:immunology; D054467:Phospholipases A2; D011247:Pregnancy
D000485:Allergens; D000911:Antibodies, Monoclonal; D001514:Bee Venoms; D007074:Immunoglobulin G; D010059:Ovomucin; D007073:Immunoglobulin E; D010741:Phospholipases A; D054467:Phospholipases A2