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.

T cell activation and function depend on Ca ²⁺ signals mediated by store-operated Ca ²⁺ entry (SOCE) through Ca ²⁺ release–activated Ca ²⁺ (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T _H 1) cell–mediated response to influenza A virus (IAV) infection and T _H 2 cell–mediated allergic airway inflammation. T cell–specific deletion of Orai1 did not exacerbate pulmonary inflammation and viral burdens following IAV infection but protected mice from house dust mite–induced allergic airway inflammation. ORAI1 controlled the expression of genes including p53 and E2F transcription factors that regulate the cell cycle in T _H 2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T _H 2 cell function. Systemic application of a CRAC channel blocker suppressed allergic airway inflammation without compromising immunity to IAV infection, suggesting that inhibition of SOCE is a potential treatment for allergic airway disease.