CD24(hi)CD27(+) B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide

Clin Exp Allergy. 2014 Apr;44(4):517-28. doi: 10.1111/cea.12238.

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.

Keywords: IL-10; allergy; asthma; human; regulatory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma / immunology*
  • Asthma / physiopathology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • CD24 Antigen / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Immunophenotyping
  • Interleukin-10 / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Phenotype
  • Respiratory Function Tests
  • Risk Factors
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Young Adult

Substances

  • CD24 Antigen
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interleukin-10