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1.
Sci Immunol ; 5(45)2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139586

RESUMO

B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.


Assuntos
Albuminas 2S de Plantas/imunologia , Antígenos de Plantas/imunologia , Linfócitos B/imunologia , Trato Gastrointestinal/imunologia , Imunoglobulina E/imunologia , Hipersensibilidade a Amendoim/imunologia , Adulto , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Ácidos Nucleicos Imobilizados/análise , Ácidos Nucleicos Imobilizados/imunologia , Masculino , Pessoa de Meia-Idade
2.
Sci Transl Med ; 11(481)2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30814336

RESUMO

Antigenic exposures at epithelial sites in infancy and early childhood are thought to influence the maturation of humoral immunity and modulate the risk of developing immunoglobulin E (IgE)-mediated allergic disease. How different kinds of environmental exposures influence B cell isotype switching to IgE, IgG, or IgA, and the somatic mutation maturation of these antibody pools, is not fully understood. We sequenced antibody repertoires in longitudinal blood samples in a birth cohort from infancy through the first 3 years of life and found that, whereas IgG and IgA show linear increases in mutational maturation with age, IgM and IgD mutations are more closely tied to pathogen exposure. IgE mutation frequencies are primarily increased in children with impaired skin barrier conditions such as eczema, suggesting that IgE affinity maturation could provide a mechanistic link between epithelial barrier failure and allergy development.


Assuntos
Doenças Transmissíveis/imunologia , Meio Ambiente , Receptores de Antígenos de Linfócitos B/metabolismo , Adulto , Envelhecimento , Anticorpos/genética , Antígenos/imunologia , Linfócitos B/imunologia , Carbanilidas , Pré-Escolar , Células Clonais , Eczema/imunologia , Características da Família , Feminino , Humanos , Hipersensibilidade/imunologia , Switching de Imunoglobulina , Imunoglobulina E/metabolismo , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Lactente , Masculino , Hipermutação Somática de Imunoglobulina , Vacinas/imunologia
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