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

Jiménez‐Saiz, Rodrigo; Ellenbogen, Yosef; Bruton, Kelly; Spill, Paul; Sommer, Doron D.; Lima, Hermenio; Waserman, Susan; Patil, Sarita U.; Shreffler, Wayne G.; Jordana, Manel

doi:10.1016/j.jaci.2019.04.001

Cited by 46 publications

(52 citation statements)

References 13 publications

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“…Moreover, comparison of IgE + ASC induction using PBMC from atopic and non-atopic donors collected at multiple time-points throughout the year, in which allergen exposure would be more or less likely, would also be informative for determining if pre-committed IgE + ASC precursors are consistently present, or whether this cell population is transiently induced in close proximity to allergen encounter. Furthermore, since detection of IgE + human memory B cells is technically challenging using a flow cytometric approach [58,59], the ability to monitor IgE responses more precisely through deliberate in vitro stimulation would constitute a breakthrough.…”

Section: Discussionmentioning

confidence: 99%

IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells

Franke

Kirchenbaum²,

Küerten

et al. 2020

Cells

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Detection of antigen-specific memory B cells for immune monitoring requires their activation, and is commonly accomplished through stimulation with the TLR7/8 agonist R848 and IL-2. To this end, we evaluated whether addition of IL-21 would further enhance this TLR-driven stimulation approach; which it did not. More importantly, as most antigen-specific B cell responses are T cell-driven, we sought to devise a polyclonal B cell stimulation protocol that closely mimics T cell help. Herein, we report that the combination of agonistic anti-CD40, IL-4 and IL-21 affords polyclonal B cell stimulation that was comparable to R848 and IL-2 for detection of influenza-specific memory B cells. An additional advantage of anti-CD40, IL-4 and IL-21 stimulation is the selective activation of IgM+ memory B cells, as well as the elicitation of IgE+ ASC, which the former fails to do. Thereby, we introduce a protocol that mimics physiological B cell activation through helper T cells, including induction of all Ig classes, for immune monitoring of antigen-specific B cell memory.

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Section: Discussionmentioning

confidence: 99%

IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells

Franke

Kirchenbaum²,

Küerten

et al. 2020

Cells

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show abstract

“…60,61 Evidence is pointing toward an extreme rarity of IgE memory B cells in peripheral blood of allergic individuals that is even more rare in non-peanut-allergic individuals. 62 This suggests the activation of pools from allergen-specific B-cell subsets, for example, from IgG1-positive allergen-specific B cells upon switch factors and stimulation. 63 Recent data on STAT3 on the regulation of antibody diversity in general and IgE specifically have added to our understanding on IgE regulation 64 and allergic inflammation.…”

Section: Pbmcs Of Milk-allergic Individuals Show a Significant Downrementioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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“…Various methods were utilized to generate allergen-specific genuine, i.e. native antibodies with the preservation of the natural VH and VL pairing including hybridoma technology, Epstein-Barr-Virus (EBV) transformation, single B cell sorting and cloning and HumAb mice (transgenic mice that produce fully human antibodies) (18,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). In parallel, versatile approaches were developed to generate non-genuine antibodies by random combination of VH and VL chains, i.e., combinatorial Fab/ScFv libraries or (semi-) synthetic libraries (37,38,(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60).…”

Section: The Complex and Laborious Approach To Identify Effective Prmentioning

confidence: 99%

Nanobodies—Useful Tools for Allergy Treatment?

2020

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In the last decade single domain antibodies (nanobodies, V H H) qualified through their unique characteristics have emerged as accepted and even advantageous alternative to conventional antibodies and have shown great potential as diagnostic and therapeutic tools. Currently nanobodies find their main medical application area in the fields of oncology and neurodegenerative diseases. According to late-breaking information, nanobodies specific for coronavirus spikes have been generated these days to test their suitability as useful therapeutics for future outbreaks. Their superior properties such as chemical stability, high affinity to a broad spectrum of epitopes, low immunogenicity, ease of their generation, selection and production proved nanobodies also to be remarkable to investigate their efficacy for passive treatment of type I allergy, an exaggerated immune reaction to foreign antigens with increasing global prevalence.

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

Cited by 46 publications

References 13 publications

IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells

IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells

Recent developments and highlights in food allergy

Nanobodies—Useful Tools for Allergy Treatment?

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