Human IgG monoclonal antibodies that modulate the binding of specific IgE to birch pollen Bet v 1.
Birch pollen allergy is a very frequent pathology in Europe and North America. More than 95% of the tree pollen allergic patients display IgE reactivity against Bet v 1, the major birch pollen allergen. Starting with PBL from a patient desensitized by immunotherapy, we have generated five B cell lines (BAB1 to BAB5) that secrete human IgG mAbs of high affinity for Bet v 1. Although competition studies indicated that these human IgG mAb recognized different epitopes, broad cross-reactivity was found with Bet v 1 homologous allergens present in tree pollens and plant-derived foods. When tested for interference with allergic patients' IgE, BAB1 inhibited (by 80-100%) the binding of IgE to nitrocellulose-blotted Bet v 1, while BAB2 enhanced it. The biologic significance of the ability of BAB1 to interfere with patients' IgE binding is indicated by the finding that BAB1 completely inhibited Bet v 1-induced histamine release from allergic patients' basophils. Allergen-specific human IgG mAbs such as BAB1, which presents high blocking activity in both immunochemical and cellular IgE competition experiments, might have therapeutical application.
Visco
V
V
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Dolecek
C
C
Denépoux
S
S
Le Mao
J
J
Guret
C
C
Rousset
F
F
Guinnepain
M T
MT
Kraft
D
D
Valenta
R
R
Weyer
A
A
Banchereau
J
J
Labecque
S
S
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D000485:Allergens / Q000187:drug effects / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D000918:Antibody Specificity; D052179:Antigens, Plant; D001491:Basophils / Q000276:immunology; D001666:Binding Sites, Antibody / Q000187:drug effects*; D001667:Binding, Competitive; D003429:Cross Reactions; D018604:Epitope Mapping; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000187:drug effects / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D010940:Plant Proteins / Q000187:drug effects / Q000378:metabolism*; D011058:Pollen / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000485:Allergens; D000911:Antibodies, Monoclonal; D052179:Antigens, Plant; D007074:Immunoglobulin G; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E