title: Inhibition of rBet v 1-induced basophil histamine release with specific immunotherapy -induced serum immunoglobulin G: no evidence that FcgammaRIIB signalling is important.
abstract: BACKGROUND
  Human basophils and mast cells express the low-affinity immunoglobulin (Ig)G receptor FcgammaRIIB. It has previously been shown in artificial model systems that cross-linking of the high-affinity IgE receptor FcepsilonRI and FcgammaRIIB leads to inhibition of FcepsilonRI signalling.
  
  
  OBJECTIVE
  The aim of the present study was to investigate whether cross-linking of FcepsilonRI and FcgammaRIIB contributes to IgG-mediated inhibition of histamine release in human basophils in a system using the sera from specific immunotherapy (SIT) patients and the major allergen from birch pollen, Bet v 1. As IgG4 furthermore has been proposed to have special blocking properties, we investigated the significance of IgG subclass specificity for this inhibition.
  
  
  METHODS
  Binding of recombinant Bet v 1-IgG complexes to FcgammaRII and IgG-binding activities in the sera from 25 birch pollen-allergic patients treated with SIT were measured using (125)I-rBet v 1. Inhibition of basophil histamine release was assessed by incubating washed leucocytes with complexes of rBet v 1-IgG with or without blocking of FcgammaRII.
  
  
  RESULTS
  We observed low binding of rBet v 1-IgG complexes to FcgammaRII, which was negatively correlated with the relative IgG4-binding activities. Blocking of FcgammaRII did not reverse the SIT-IgG-induced inhibition of basophil histamine release. However, IgG-binding activities correlated significantly with the ability of the SIT sera to inhibit basophil histamine release.
  
  
  CONCLUSIONS
  We suggest that at least in birch pollen SIT, the contribution of FcgammaRIIB-mediated inhibitory signalling to SIT-IgG-induced inhibition of human basophil histamine release is of minor importance. The main contributor to the inhibitory effect of SIT-induced IgG seems to be blocking of the allergen-IgE interaction.
authors.affiliation: ALK-Abelló, Bøge Alle, Hørsholm, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Ejrnaes
authors.forename: M
authors.initials: M
authors.lastname: Svenson
authors.forename: G
authors.initials: G
authors.lastname: Lund
authors.forename: J N
authors.initials: JN
authors.lastname: Larsen
authors.forename: H
authors.initials: H
authors.lastname: Jacobi
mesh_terms: D000485:Allergens / Q000276:immunology*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000276:immunology; D052179:Antigens, Plant; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D017452:Receptors, IgG / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000485:Allergens; D000936:Antigen-Antibody Complex; D052179:Antigens, Plant; C499173:FCGR2B protein, human; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011994:Recombinant Proteins; D007073:Immunoglobulin E