Pathogenic IgE-fated B cell memory retains functional plasticity

Abstract

Long-lived immunoglobulin (Ig) E responses against innocuous environmental and dietary antigens (Ags) are maintained by an IgG1-dominant memory B cell (MBC) compartment primed for IL-4 responsiveness. In this work, we investigated the plasticity of the MBC compartment fated for IgE class switch recombination upon Ag re-exposure. Antibody-mediated IL-4R( blockade augmented the germinal center response and uncovered an IL-4/IL-13 dependency within the type 2 memory B cell (MBC2) skewed phenotype. In the absence of IL-4/IL-13 signaling during the recall response, a long-lived Ag-specific IgG2c MBC population emerged, shifting the MBC response away from a type 2 phenotype and towards type 1. The emergence of this IgG2c response was dependent on IFN-( signaling and arose from both unswitched and class-switched Ag-specific B cells in vivo. We further demonstrated that a type 1-polarizing adjuvant can augment the redirection of type 2-polarized class-switched MBCs, suggesting with the correct cues pathogenic MBCs can be functionally reprogrammed.One Sentence SummaryB cell responses to allergens can be reprogrammed away from a pathogenic fate through IL-4/IL-13 signaling blockade.