B cell-intrinsic Toll-like receptor 9 signaling restrains IgE responses

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B694
Abstract ID: 4512

Presenting Author:
Karen Chang , Graduate Student at Loyola Univ. Chicago

Abstract:

Allergen-specific IgE mediates allergic diseases. B cells produce IgE through class switch recombination (CSR), a process driven by T cell help and the Th2 cytokine IL-4. Early life exposure to microbial products is associated with lower IgE levels. To investigate how microbial products shape IgE responses, we administered a synthetic Toll-like receptor 9 agonist (CpG) that mimics microbial DNA in a mouse model of allergic asthma. We found that CpG administration prior to allergen re-exposure reduced IgE levels as well as CSR to IgE. To interrogate how B cell-intrinsic TLR9 signaling modulates CSR to IgE, we cultured resting mouse B cells with anti-CD40 antibody and IL-4 with or without CpG. CpG reduced IgE CSR and germline transcription at Iε, a prerequisite for IgE CSR. It was previously shown that overexpression of the transcription factor C/EBPβ inhibited Iε transcription in mouse B cell lines. We performed western blot analyses on primary mouse B cells and revealed that CpG upregulates C/EBPβ with anti-CD40 and IL-4. This effect depends on TLR9 and MYD88 as upregulation of C/EBPβ by CpG was abrogated in TLR9- or MYD88-deficient B cells. Additionally, TLR9- and MYD88-deficient B cells expressed higher endogenous levels of C/EBPβ, which correlated with lower levels of CSR to IgE compared to WT cells. Altogether, our data suggest that C/EBPβ restrains IgE CSR downstream of TLR9 signaling in B cells.