CD23 <sup>+</sup> IgG1 <sup>+</sup> memory B cells are poised to switch to pathogenic IgE production in food allergy
Miyo Ota, Kenneth B. Hoehn, Weslley Fernandes‐Braga, Takayuki Ota, Carlos J. Aranda, Sara L. Friedman, Mariana G. C. Miranda-Waldetario, Jamie Redes, Maria Suprun, Galina Grishina, Hugh A. Sampson, Alefiyah Malbari, Steven H. Kleinstein, Scott H. Sicherer, Maria A. Curotto de Lafaille
Abstract
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.