Tobias Rogosch - IgE transcripts in the circulation of allergic children reflect a classical antigen-driven B cell response and not a superantigen-like activation.

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  Publication Details (including relevant citation   information):

  Kerzel S, Rogosch T, Struecker B, Maier RF, Zemlin M.

  J Immunol. 2010 Aug 15;185(4):2253-60

  doi: 10.4049/jimmunol.0902942


  Allergic asthma is the most frequent chronic disorder in   childhood.  Although IgE is a central effector molecule in   allergic diseases, the  nature of the IgE response is still   under debate. The objective of our  study was to clarify   whether the IgE repertoire in the circulation of  allergic   children represents a classical Ag-driven and oligoclonal B    cell response, a superantigen-like activation of a subset of B   cells, or  a polyclonal B-1 cell expansion. Using a highly   sensitive RT-PCR  method, we amplified, cloned, and   sequenced IgE H chain transcripts from  13 children with   allergic asthma. We gained 1366 functional IgE  sequences,   which currently represent the most extensive collection of    human IgE transcripts. Compared to IgM transcripts from the   same  children, the somatic mutation rate was significantly   enhanced in IgE  transcripts (21 per thousand versus 72 per   thousand; p < 0.001),  which renders a polyclonal B-1   response unlikely. Moreover, IgE  sequences displayed   significantly enhanced Ag selection and hence were    indicative of a classical Ag-driven immune response with   affinity  maturation (p < 0.001). In contrast to several   recent studies, the  usage pattern of variable gene segment   of the H Ig chain in IgE  transcripts followed the germline   complexity, arguing against a  superantigen-like   interaction. We conclude that IgE transcripts in the    circulation of children with allergic asthma reflect a   classical  adaptive B-2 cell response. This study provides   reference data for a  better characterization of the IgE   response under immunomodulating  therapies, such as anti-IgE   therapy or allergen-specific immunotherapy.

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