期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 11, 期 481, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aat2004
关键词
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资金
- Stanford Center for Clinical and Translational Education and Research (SCCTER) NIH from the National Center for Research Resources [1UL1 RR025744]
- NIH [U19 AI090019, R01 HD063142, 1R01 AI125567]
- Ellison Medical Foundation
- Child Health Research Institute
- Stanford NIH-NCATS-CTSA [UL1 TR001085]
- Crown Family Foundation
- Li Ka Shing Foundation
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.
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