title: An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of FcepsilonRI with FcgammaRIIb.
abstract: BACKGROUND
  IgE binds to mast cells and basophils via its high-affinity receptor, FcepsilonRI, and cross-linking of FcepsilonRI-bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross-linking of FcepsilonRI with FcgammaRIIb, an ITIM-containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti-idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to FcepsilonRI-bound IgE, via its Fab regions, and the negative regulatory receptor, FcgammaRIIb, via its Fc region.
  
  
  OBJECTIVE
  To assess the ability of human 2G10 to inhibit anti-IgE and allergen-driven basophil degranulation through cross-linking of FcepsilonRI-bound IgE with FcgammaRIIb.
  
  
  METHODS
  2G10 was assessed for its ability to bind to FcgammaRIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti-IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL-4 expression intracellularly, using flow cytometery.
  
  
  RESULTS
  Human 2G10 was able to bind to FcgammaRIIb on transfected cells and on purified basophils, and induce a dose-dependent inhibition of both anti-IgE and Der p 1-driven degranulation of basophils.
  
  
  CONCLUSIONS
  The inhibition of basophil degranulation by the human IgG1 anti-idiotype 2G10 highlights the therapeutic potential of IgE-reactive IgG antibodies in restoring basophil integrity through recruitment of the inhibitory receptor FcgammaRIIb.
authors: School of Molecular Medical Sciences, Institute of Infection, Immunity and Inflammation, University of Nottingham, Nottingham, UK.
authors: S J
authors: SJ
authors: Wigginton
authors: P B
authors: PB
authors: Furtado
authors: K L
authors: KL
authors: Armour
authors: M R
authors: MR
authors: Clark
authors: A
authors: A
authors: Robins
authors: M
authors: M
authors: Emara
authors: A M
authors: AM
authors: Ghaemmaghami
authors: H F
authors: HF
authors: Sewell
authors: F
authors: F
authors: Shakib
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects* / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects*; D020740:Chimerin Proteins / Q000276:immunology / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D017455:Receptors, IgE / Q000187:drug effects* / Q000276:immunology; D017452:Receptors, IgG / Q000187:drug effects* / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D020740:Chimerin Proteins; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1