Tobias Rogosch - Plasma cells and nonplasma B cells express differing IgE repertoires in allergic sensitization.

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  Publication Details (including relevant citation   information):

  Rogosch T, Kerzel S, Sikula L, Gentil K, Liebetruth M,   Schlingmann KP, Maier RF, Zemlin M.

  J Immunol. 2010 May 1;184(9):4947-54

  doi: 10.4049/jimmunol.0900859


  The selection of allergen-specific B cells into the plasma cell   (PC)  pool is a critical step in the immune dysregulation   that leads to the  production of IgE in allergic diseases.   We sought to characterize the  murine IgE repertoire. In   particular, we questioned whether the IgE  repertoire of   plasmablasts (PBs)/PCs differs from the IgE repertoire of    non-PCs. Therefore, we sorted splenocytes from OVA-sensitized   BALB/c  mice into CD138(pos) (PBs/PCs) and   CD19(pos)/CD138(neg) (non-PCs) B cell  fractions. Using   reverse transcription PCR, we amplified, cloned, and    sequenced IgE mRNA transcripts and analyzed the Ig H chain   repertoire.  As a reference, we characterized the IgM   repertoire of the same animals.  Compared to IgM, the IgE   sequences contained a significantly higher  level of somatic   mutations and displayed an oligoclonal expansion with    clonotype restriction. Interestingly, we found two   phenotypically  distinct IgE-producing B cell subpopulations   that differed in their  repertoire of H chain transcripts;   IgE transcripts from PBs/PCs showed  significantly more   signs of Ag-driven selection than transcripts from  non-PCs,   including 1) a higher number of somatic mutations, 2)   increased  clustering of replacement mutations in the CDRs,   and 3) biased third  CDR of the heavy Ig chain composition.   In conclusion, PBs/PCs and  non-PCs from OVA-sensitized mice   express distinct IgE repertoires,  suggesting that 1) the   repertoire of IgE-expressing PBs/PCs represents a  highly   biased selection from the global B cell repertoire and 2)    Ag-driven affinity maturation is a major force that selects    IgE-producing B cells into the CD138(pos) PC pool.

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