title: The majority of allergen-specific IgE in the blood of allergic patients does not originate from blood-derived B cells or plasma cells.
abstract: BACKGROUND
  The production of allergen-specific IgE antibodies is a hallmark of IgE-mediated allergy but the contribution of blood cells to allergen-specific IgE production in allergic patients has not been studied in detail.
  
  
  OBJECTIVE
  Aim of this study was the characterization of IgE-producing cells in the blood of allergic patients and the determination of the amount of IgE antibodies which are produced by these cells in relation to total amounts of circulating specific IgE.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) were isolated from allergic patients and cell populations were purified or depleted using magnetically labelled antibodies directed against specific cell surface markers (CD19, CD20, CD22, CD27, CD38, CD126, CD138, CD203c). Allergen-specific IgE was measured in serum samples and cell culture supernatants by quantitative ImmunoCAP measurements and by ELISA using purified recombinant allergens. IgE transcripts were detected using RT-PCR with primers specific for human IgE.
  
  
  RESULTS
  We found that allergen-specific IgE levels in PBMC supernatants correlated strongly with specific serum IgE but represented less than 1% of circulating IgE. Depletion of basophils resulted in substantial reduction of allergen-specific IgE levels in PBMC culture supernatants suggesting that an important source of allergen-specific IgE in PBMC supernatants could be IgE derived from the surface of basophils. Newly synthesized IgE was derived from CD138+ plasma cells, but not from B and B memory cells, and accounted for only approximately 0.2% of circulating IgE in blood.
  
  
  CONCLUSIONS
  Our finding that the majority of allergen-specific IgE in the peripheral blood is not derived from IgE-secreting cells in the blood suggests local IgE production in tissues as a major source for allergen-specific IgE and possible target for therapeutic intervention.
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Eckl-Dorna
authors.forename: I
authors.initials: I
authors.lastname: Pree
authors.forename: J
authors.initials: J
authors.lastname: Reisinger
authors.forename: K
authors.initials: K
authors.lastname: Marth
authors.forename: K-W
authors.initials: KW
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Vrtala
authors.forename: S
authors.initials: S
authors.lastname: Spitzauer
authors.forename: R
authors.initials: R
authors.lastname: Valenta
authors.forename: V
authors.initials: V
authors.lastname: Niederberger
mesh_terms: D000485:Allergens / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology*; D053668:Syndecan-1 / Q000378:metabolism
chemical_list: D000485:Allergens; C508241:SDC1 protein, human; D053668:Syndecan-1; D007073:Immunoglobulin E