Asthmatic subjects with allergy have elevated levels of IgE+ B cells in the airways

Abstract

Disclosure of potential conflict of interest: A. Asarnoj has received travel support from MEDA; serves as a consultant for MEDA; and received payments for lectures from ThermoFisher. C. Lupinek receives payment for lectures from ThermoFisher. J. M. Anto receives grant support from EU FP7 MeDALL. J. Bousquet serves on the advi

Human BCR analysis of single-sorted, putative IgE+ memory B cells in food allergy

“…1 In stark contrast, several human studies have claimed that a population of IgE 1 MBCs can be identified in PBMCs of healthy donors, atopic donors, and donors with food allergy, [2][3][4] as well as in the sputum of asthmatic patients. 5,6 Moreover, the presence of these cells in the circulation has been proposed as a prognostic marker of allergy. 2 Divergent findings on the existence of IgE-expressing MBCs between mice and human subjects could be partly due to the precision of techniques used in their quantification.…”

“…Reported frequencies of IgE-expressing MBCs in peripheral blood vary depending on the flow cytometric identification strategies. 2,3,6,8 A basic approach to identify these cells involves intracellular staining of IgE without preventing staining of cytotropic IgE. 5,6 A more stringent detection method involves the stepwise exclusion of each BCR isotype through extracellular staining.…”

BCR analysis of single-sorted, putative IgE+memory B cells in food allergy:an ephemeral existence?

“…In murine systems, flow cytometry, immunofluorescence, genetic analysis, in vitro cultures, IgE reporter mice and functional models of adoptive transfer (17,18,21,(36)(37)(38) have been used to study IgE + MBCs. In humans, putative IgE + MBCs have been studied mainly by flow cytometry (24,27,28), occasionally validated via genetic analysis in bulk (14) to roughly infer the frequency of the different BCR-transcripts expression in B cell populations (39). However, increasing evidence in mice and humans has questioned the relevance, even the existence, of IgE + MBCs as the true reservoir of IgE-secreting cells (8,15,19,20,31,40).…”

“…Reported frequencies of IgE-expressing MBCs in peripheral blood vary depending on the flow cytometric identification strategies (14,24,27,28,30,31). A basic approach to identify these cells involves intracellular staining of IgE without preventing staining of cytotropic IgE (27,28). A more stringent detection method was reported by Berkowska et al (14), which involves the stepwise exclusion of each BCR isotype via extracellular staining.…”

“…The body of data from murine models demonstrates that IgE + MBCs are extremely rare, at best, therefore suggesting that IgE-mediated recall responses are derived from non-IgE expressing MBCs, particularly IgG1 (8,22,23). In stark contrast, several human studies have claimed that a population of IgE + MBCs can be identified in peripheral blood mononuclear cells (PBMCs) of healthy, atopic and food-allergic donors (14,(24)(25)(26), as well as in the sputum of asthmatics (27,28). Moreover, the presence of these cells in circulation has been proposed as a prognostic marker of allergy (24).…”