Main idea: For the first time, it was shown that on mucosal allergen exposure human IgE memory resides in allergen-specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+immune cells and serve as a potential target for therapeutic intervention.
IgE is the least abundant immunoglobulin, which is tightly regulated. IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood.
The objective of the study was to evaluate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT).
In a randomized double-blind, placebo-controlled, time course sublingual immunotherapy study Peripheral blood mononuclear cells and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks.
Results: Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgE+ immune cells and IgG+ memory B cells. Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared to be relatively stable as per heavy chain isotype, somatic hypermutations, and clonal composition.