The B-cell antigen receptor of IgE-switched plasma cells regulates memory IgE responses

• Published in: Journal of allergy and clinical immunology Vol. 146; no. 3; pp. 642 - 651.e5
• Main Authors: Schmitt, Michaela E.R., Lutz, Johannes, Haase, Paul, Bösl, Michael R., Wienands, Jürgen, Engels, Niklas, Voehringer, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2020
• Subjects: Allergens - immunology; Allergy; Animals; B-cell receptor; Chymases - immunology; Female; helminths; IgE; Immunoglobulin E - immunology; Immunologic Memory; Male; Mast Cells - immunology; Mice, Transgenic; Ovalbumin - immunology; plasma cells; Plasma Cells - immunology; Receptors, Antigen, B-Cell - immunology; Trichostrongyloidea; Trichostrongyloidiasis - immunology; Allergy; CSR; mIgE-YF; IgE; ITT; mIgE; plasma cells; B-cell receptor; MLN; BCR; PC; PE; CY; mIgG1; OVA; helminths; EMPD; GC
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2020.02.015

Allergic inflammation is driven by IgE-producing plasma cells (PCs), which are required for IgE-mediated activation of mast cells and basophils. Repeated antigen encounter elicits a memory IgE response with elevated serum IgE titers and accumulation of IgE-producing PCs. However, the cellular compartment and molecular signals that underlie the immunologic memory of IgE responses remain unclear.
With this study we aimed at clarifying whether inactivation of the cytoplasmic immunoglobulin tail tyrosine (ITT) motif in transmembrane IgE (mIgE) impairs the memory IgE response in mice.
We generated mice with an inactivated mIgE-ITT motif and analyzed serum IgE levels as well as the generation of IgE-producing germinal center B cells and PCs subsequent to primary and secondary infection with helminths. In vitro cultures were used to study the mIgE-ITT–controlled expression of mIgE on the surface of PCs. Systemic mast cell activation was determined by serum Mcpt1 ELISA in response to ovalbumin challenge.
mIgE-ITT–mutant mice showed an impaired memory IgE response subsequent to helminth infection. Furthermore, sensitization and challenge of mIgE-ITT–mutant mice with ovalbumin resulted in diminished serum IgE titers and reduced mast cell activation. The mIgE-ITT motif was required for optimal cell surface expression of mIgE B-cell antigen receptors but not for intracellular IgE expression in PCs.
These results indicate that the mIgE B-cell antigen receptor plays a critical role in establishing or maintaining the population of IgE-producing PCs during memory IgE responses.
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