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Peanut oral immunotherapy transiently expands circulating Ara h 2–specific B cells with a homologous repertoire in unrelated subjects

Author(s)
Calatroni, Agustin; Tadigotla, Vasisht R.; Ruiter, Bert; Ma, Alex; Moon, James; Shreffler, Wayne G.; Patil, Sarita; Ogunniyi, Adebola Oluwakayode; Love, John C; ... Show more Show less
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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
Date issued
2015-05
URI
http://hdl.handle.net/1721.1/109437
Department
Massachusetts Institute of Technology. Department of Chemical Engineering; Koch Institute for Integrative Cancer Research at MIT
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.
Version: Author's final manuscript
ISSN
0091-6749

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