The memory of pathogenic IgE is contained within CD23+IgG1+ memory B cells poised to switch to IgE in food allergy

Ota, M.; Hoehn, K.; Ota, T.; Aranda, C.; Friedman, S.; Braga, W.; Malbari, A.; Kleinstein, S.; Sicherer, S.; Curotto de Lafaille, M.

doi:10.1101/2023.01.25.525506

bioRxiv · 10.1101/2023.01.25.525506

The memory of pathogenic IgE is contained within CD23+IgG1+ memory B cells poised to switch to IgE in food allergy

Ota, M.·Hoehn, K.·Ota, T.·Aranda, C.·Friedman, S.·Braga, W.·Malbari, A.·Kleinstein, S.·Sicherer, S.·Curotto de Lafaille, M.

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Abstract

Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23+IgG1+ memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These type2-marked IgG1+ memory B cells differentially express IL-4/IL-13 regulated genes FCER2/CD23, IL4R, and germline IGHE and carry highly mutated B cell receptors (BCRs). Further, high affinity memory B cells specific for the main peanut allergen Ara h 2 mapped to the population of type2-marked IgG1+ memory B cells and included 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 pathogenic IgE. One-Sentence SummaryWe describe a unique population of IgG+ memory B cells poised to switch to IgE that contains high affinity allergen-specific clones in peanut allergy.

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Ota, M., Hoehn, K., Ota, T., Aranda, C., Friedman, S., Braga, W., Malbari, A., Kleinstein, S., Sicherer, S., Curotto de Lafaille, M.. 2023-01-25. The memory of pathogenic IgE is contained within CD23+IgG1+ memory B cells poised to switch to IgE in food allergy. https://doi.org/10.1101/2023.01.25.525506

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