Peanut oral immunotherapy transiently expands circulating Ara h 2–specific B cells with a homologous repertoire in unrelated subjects
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Love_Peanut oral.pdf
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Author(s)
Calatroni, Agustin
Tadigotla, Vasisht R.
Ruiter, Bert
Ma, Alex
Moon, James
Shreffler, Wayne G.
Patil, Sarita
Ogunniyi, Adebola Oluwakayode
Love, John C
Date Issued
May 2015
Journal
Journal of Allergy and Clinical Immunology
Publisher
Elsevier
Citation
Patil, Sarita U.; Ogunniyi, Adebola O.; Calatroni, Agustin; Tadigotla, Vasisht R.; Ruiter, Bert; Ma, Alex; Moon, James; Love, J. Christopher and Shreffler, Wayne G. “Peanut Oral Immunotherapy Transiently Expands Circulating Ara h 2–specific B Cells with a Homologous Repertoire in Unrelated Subjects.” Journal of Allergy and Clinical Immunology 136, no. 1 (July 2015): 125–134.e12 © 2015 American Academy of Allergy, Asthma & Immunology.
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Author's final manuscript
Abstract
Background
Peanut oral immunotherapy (PNOIT) induces persistent tolerance to peanut in a subset of patients and induces specific antibodies that might play a role in clinical protection. However, the contribution of induced antibody clones to clinical tolerance in PNOIT is unknown.
Objective
We hypothesized that PNOIT induces a clonal, allergen-specific B-cell response that could serve as a surrogate for clinical outcomes.
Methods
We used a fluorescent Ara h 2 multimer for affinity selection of Ara h 2–specific B cells and subsequent single-cell immunoglobulin amplification. The diversity of related clones was evaluated by means of next-generation sequencing of immunoglobulin heavy chains from circulating memory B cells with 2x250 paired-end sequencing on the Illumina MiSeq platform.
Results
Expression of class-switched antibodies from Ara h 2–positive cells confirms enrichment for Ara h 2 specificity. PNOIT induces an early and transient expansion of circulating Ara h 2–specific memory B cells that peaks at week 7. Ara h 2–specific sequences from memory cells have rates of nonsilent mutations consistent with affinity maturation. The repertoire of Ara h 2–specific antibodies is oligoclonal. Next-generation sequencing–based repertoire analysis of circulating memory B cells reveals evidence for convergent selection of related sequences in 3 unrelated subjects, suggesting the presence of similar Ara h 2–specific B-cell clones.
Conclusions
Using a novel affinity selection approach to identify antigen-specific B cells, we demonstrate that the early PNOIT-induced Ara h 2–specific B-cell receptor repertoire is oligoclonal and somatically hypermutated and shares similar clonal groups among unrelated subjects consistent with convergent selection.
Key words
Immunotherapy; antigen-specific B cells; peanut allergy; food allergy; antibody repertoire
Abbreviations used
APC, Allophycocyanin; BCR, B-cell receptor; CDR, Complementarity-determining region; NGS, Next-generation sequencing; OIT, Oral immunotherapy; PNOIT, Peanut oral immunotherapy
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.jaci.2015.03.026
