Plasma cells and not memory cells, constitute the majority of human IgE Cells

Abstract

Abstract Immunoglobulin E (IgE) is central in allergy pathology as it binds high-affinity receptors on mast cells, inducing degranulation upon allergen crosslinking. However, IgE has the lowest serum concentration and shortest half-life of all Ig’s, and IgE+ B cells are extremely rare. This work aims to uncover characteristics of IgE+B cells that could be used in the design of new therapeutic strategies for allergic diseases. IgE+ cells were identified in Atopic Dermatitis (AD) patients, and were also generated in vitro by stimulating with aCD40 and IL-4. Naïve, IgG+, IgA+ and IgE+ cells from AD donors were phenotyped and sorted by flow cytometry, and their transcriptomes were determined by RNAseq. Inter-sample similarity was determined using multidimensional scaling (MDS). Gene ontology (GO) of differentially expressed genes (DEG) identified molecular pathways enriched in IgE+ cells. IgE+ cells were CD38hiCD27hi, indicating a high content of plasma cells in IgE+ B cells. IgE+ cells expressed high levels of proliferation marker Ki67. MDS comparison of datasets of naïve, IgG+, IgA+ and IgE+ cells showed that IgE cells were distant from both IgG and IgA cells. GO analysis of IgE DEG demonstrated that IgE cells expressed genes associated with N-glycosylation, the IRE1-XBP1 endoplasmic reticulum unfolded protein response, and mitochondrial oxidative phosphorylation, synonymous with plasma cells. Our data indicates that IgE+ cells in AD patients are predominantly plasmablasts and plasma cells, and not memory B cells. Ongoing studies aim to characterize human IgE cell diversity using single cell analysis, and to identify non-IgE precursor memory cells that give rise to IgE+ cells upon allergen activation.