Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B cells with a homologous repertoire in unrelated subjects.
J Allergy Clin Immunol
; 136(1): 125-134.e12, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25985925
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Glicoproteínas
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Dessensibilização Imunológica
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Hipersensibilidade a Amendoim
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Antígenos de Plantas
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Albuminas 2S de Plantas
Limite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2015
Tipo de documento:
Article