title: CD24(hi)CD27(+) B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide.
abstract: BACKGROUND
  Regulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma.
  
  
  OBJECTIVE
  In this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated.
  
  
  METHODS
  Isolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4(+) T cells and house dust mite allergen DerP1.
  
  
  RESULTS
  Lower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24(hi)CD27(+) B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4(+) T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24(hi)CD27(+) B cells are responsible for the induction of IL-10(+) CD4(+) T cells.
  
  
  CONCLUSIONS
  Taken together, these data indicate that CD24(hi)CD27(+) B cells from allergic asthma patients produce less IL-10 in response to LPS leading to a weaker IL-10 induction in T cells in response to DerP1, which may play a role in allergic asthma.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L E P M
authors.initials: LE
authors.lastname: van der Vlugt
authors.forename: E
authors.initials: E
authors.lastname: Mlejnek
authors.forename: A
authors.initials: A
authors.lastname: Ozir-Fazalalikhan
authors.forename: M
authors.initials: M
authors.lastname: Janssen Bonas
authors.forename: T R
authors.initials: TR
authors.lastname: Dijksman
authors.forename: L A
authors.initials: LA
authors.lastname: Labuda
authors.forename: R
authors.initials: R
authors.lastname: Schot
authors.forename: B
authors.initials: B
authors.lastname: Guigas
authors.forename: G M
authors.initials: GM
authors.lastname: Möller
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: M
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.forename: H H
authors.initials: HH
authors.lastname: Smits
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012129:Respiratory Function Tests; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D055815:Young Adult
chemical_list: D051927:CD24 Antigen; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10
keywords: IL-10; allergy; asthma; human; regulatory B cells