Imperial College London
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ProfessorMohamedShamji

Faculty of Medicine, National Heart & Lung Institute

Professor of Immunology and Allergy
 
 
 
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Contact

 

+44 (0)20 7594 3476m.shamji99 Website

 
 
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Location

 

Room 111Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hoof:2020:10.1016/j.jaci.2019.11.046,
author = {Hoof, I and Schulten, V and Layhadi, JA and Stranzl, T and Christensen, LH and de, la Mata SH and Seumois, G and Vijayanand, P and Lundegaard, C and Niss, K and Lund, A and Ahrenfeldt, J and Holm, J and Steveling, E and Sharif, H and Durham, SR and Peters, B and Shamji, MH and Andersen, PS},
doi = {10.1016/j.jaci.2019.11.046},
journal = {Journal of Allergy and Clinical Immunology},
pages = {180--191},
title = {Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses},
url = {http://dx.doi.org/10.1016/j.jaci.2019.11.046},
volume = {146},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Immunoglobulin E (IgE) are least abundant, tightly regulated and IgE producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood. OBJECTIVE: To investigate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT). METHODS: In a randomized double-blind, placebo-controlled, time-course SLIT study, peripheral blood mononuclear cells (PBMCs) and nasal biopsies were collected from forty adults with seasonal allergic rhinitis at baseline, 4, 8, 16, 28 and 52 weeks. RNA was extracted from PBMCs, sorted B cells and nasal biopsies for VH repertoire sequencing. Moreover, monoclonal antibodies were derived from single B cell transcriptomes. RESULTS: Combining VH repertoire sequencing and single cell transcriptomics yielded direct evidence of a parallel boost of two clonally and functionally related B cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells (termed IgGE). Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relative stable as per heavy chain isotype, somatic hypermutations and clonal composition. Single IgGE + memory B cell and IgE+ pre-plasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and were able to elicit basophil activation at very low allergen concentrations. CONCLUSION: For the first time, we have shown that upon mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These rapidly switch isotype and expand into short-lived IgE+ plasmablasts and serve as a potential target for therapeutic intervention.
AU  - Hoof,I
AU  - Schulten,V
AU  - Layhadi,JA
AU  - Stranzl,T
AU  - Christensen,LH
AU  - de,la Mata SH
AU  - Seumois,G
AU  - Vijayanand,P
AU  - Lundegaard,C
AU  - Niss,K
AU  - Lund,A
AU  - Ahrenfeldt,J
AU  - Holm,J
AU  - Steveling,E
AU  - Sharif,H
AU  - Durham,SR
AU  - Peters,B
AU  - Shamji,MH
AU  - Andersen,PS
DO  - 10.1016/j.jaci.2019.11.046
EP  - 191
PY  - 2020///
SN  - 0091-6749
SP  - 180
TI  - Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2019.11.046
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31883847
UR  - http://hdl.handle.net/10044/1/76213
VL  - 146
ER  -
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