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Sci Transl Med. 2019 Feb 27;11(481). pii: eaat2004. doi: 10.1126/scitranslmed.aat2004.

Shaping of infant B cell receptor repertoires by environmental factors and infectious disease.

Author information

1
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
2
Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA.
3
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
4
Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
5
Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
6
Stanford Blood Center, Palo Alto, CA 94304, USA.
7
Department of Biomedical Data Sciences, Stanford University, Stanford, CA 94305, USA.
8
Department of Statistics, Stanford University, Stanford, CA 94305, USA.
9
Department of Medicine, Stanford University, Stanford, CA 94305, USA.
10
Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
11
Department of Medicine, Stanford University, Stanford, CA 94305, USA. sboyd1@stanford.edu parsonnt@stanford.edu.
12
Department of Health Research and Policy, Stanford University, Stanford, CA 94305, USA.
13
Department of Pathology, Stanford University, Stanford, CA 94305, USA. sboyd1@stanford.edu parsonnt@stanford.edu.

Abstract

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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