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Products: Peanuts
Subject: Allergy

CD23+IgG1+ memory B cells are poised to switch to pathogenic IgE production in food allergy

Authors: Ota, M., Hoehn, K. B., Fernandes-Braga, W., Ota, T., Aranda, C. J., Friedman, S., Miranda-Waldetario, M. G. C., Redes, J., Suprun, M., Grishina, G., Sampson, H. A., Malbari, A., Kleinstein, S. H., Sicherer, S. H., & Curotto de Lafaille, M. A.
  • Journals: Science Translational Medicine
  • Pages: eadi0673
  • Volume: 16(733)
  • Year: 2024
Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23+IgG1+ memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23+IgG1+ memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of "type 2-marked" IgG1+ memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)- and IL-13-regulated genes, such as FCER2/CD23+, IL4R, and germline IGHE, and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of "type 2-marked" IgG1+ memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23+IgG1+ memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy.