CD23+ IgG1+ Memory B Cells Are Poised to Switch to Pathogenic IgE Production in Food Allergy
Year: 2024
Type: conference-abstract
Abstract: To understand the mechanisms underlying persistent peanut allergy in pediatric peanut-allergic patients.Peanut-allergic children were recruited from the Food Allergy Clinic at Mount Sinai Hospital with no prior history of immunotherapy or biologic treatment of allergies and did not suffer from immunodeficiency, autoimmunity, cancer, or any life-threatening infectious disease. Peanut-allergic patients were stratified into 2 groups: (1) patients with high peanut-specific IgE (>100 kU/L) designated as the persistent allergy group and (2) patients with low levels of peanut-specific (<5 kU/L) designated as the possible allergy-outgrowing group. Nonallergic pediatric controls without any history of atopic disease were recruited from the General Pediatrics clinic at Mount Sinai Hospital.This was a noninterventional study examining memory B cell populations related to persistent peanut allergy. Blood samples were collected on 58 peanut-allergic pediatric patients and 13 nonallergic pediatric controls between 2019 and 2023. Analysis was performed on PBMCs. Phenotypic and transcriptional analysis of total memory B cells were performed to characterize allergen-specific memory B cells. Functional analysis was performed to identify the memory population containing peanut-specific clones and determine the ability of memory cells to switch to IgE.A significantly higher percentage of CD23+ (low affinity IgE receptor) memory B cells were isolated in peanut-allergic children than nonallergic children. In peanut-allergic children, the frequency of CD23 + IgG + memory B cells correlated with circulating total IgE concentration. A population of “type 2-marked” IgG1 + B cells differentially expressed IL-4 and IL-13 regulated genes, such as FCER2/CD23+, IL4R, and germline IGHE, and carried highly mutated B cell receptors. In peanut-allergic children with elevated serum peanut-specific IgE, high-affinity B cells binding the main peanut allergen Ara h2 were mapped to the “type 2-marked” IgG1 + memory B cells and included clones expressing genes that were primed to switch to IgE.In pediatric patients with peanut allergy, there was a population of somatically mutated IgG + memory B cells expressing genes commonly implicated in atopic disease. This memory B cell population also contained high-affinity peanut-specific clones and were poised to switch to IgE. These cells were enriched in children with peanut allergy compared with nonallergic pediatric controls.IgE is an important player in food allergy and other allergic responses, but most IgE-producing cells are typically short-lived. This paper describes a population of memory B cells with highly mutated B cell receptors specific to peanuts poised to switch to IgE. This population is most likely the source of pathogenic, allergen-specific cells that replenish the IgE-producing cell pool mediating persistent peanut allergy and may serve as a potential target for future immunotherapy.
Source: PEDIATRICS
Authors: Maria Lee, Sara Anvari
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404924909