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Allergen extract-induced interleukin-10 in human memory B cells inhibits immunoglobulin E production

Authors

  • M. Milovanovic,

    1. Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité– Universitätsmedizin Berlin, Berlin, Germany
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    • 1Contributed equally to this work.

  • G. Heine,

    1. Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité– Universitätsmedizin Berlin, Berlin, Germany
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    • 1Contributed equally to this work.

  • T. Zuberbier,

    1. Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité– Universitätsmedizin Berlin, Berlin, Germany
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  • M. Worm

    1. Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité– Universitätsmedizin Berlin, Berlin, Germany
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Correspondence:
Prof. Dr. Margitta Worm, Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité– Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
E-mail: margitta.worm@charite.de

Summary

Background Elevated specific IgE antibody levels are common in atopic individuals, caused by T-helper type 2-dominated B cell activation. The induction of antigen-specific IL-10 secreting T cells is discussed as an important mechanism during specific immunotherapy. By contrast the presence and function of B cell-derived IL-10 is not well defined yet.

Objective We investigated whether type-I allergen extracts induce IL-10 expression in human B cells and analysed its functional role on IgE production.

Methods Human peripheral B cells were stimulated with grass pollen, house dust mite (HDM) (Dermatophagoides pteronyssimus; Der p) and dog allergen extract. Expression of IL-10 by activated human B cells was determined by flow cytometric analysis and ELISA. Functional analysis considering immunoglobulin production was assayed by ELISA.

Results The allergen extracts studied induced IL-10 expression in B cells. However, the ability to induce IL-10 differed between the allergen extracts. The most potent allergen extract was dog (169±28 pg/mL), followed by grass pollen (141±10 pg/mL) and HDM allergen (125±11 pg/mL). Upon allergen extract stimulation only CD27 expressing memory B cells produced IL-10 and co-expressed the very early activation antigen CD69. The addition of allergen extracts to B cells activated by anti-CD40 and IL-4 selectively inhibited IgE which was dependent on allergen extract-induced IL-10. By contrast the other immunoglobulin subclasses like IgA, IgG or IgM were not altered upon allergen extract challenge.

Conclusion Our data indicate that allergen-activated memory B cells can modulate IgE production through secretion of IL-10.

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