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

2019; American Association for the Advancement of Science; Volume: 11; Issue: 481 Linguagem: Inglês

10.1126/scitranslmed.aat2004

1946-6242

Sandra C. A. Nielsen, Krishna M. Roskin, Katherine Jackson, Shilpa A. Joshi, Parastu Nejad, Ji-Yeun Lee, Lisa E. Wagar, Tho D. Pham, Ramona A. Hoh, Khoa D. Nguyen, Hannah Tsunemoto, Sonal B. Patel, Robert Tibshirani, Catherine Ley, Mark M. Davis, Julie Parsonnet, Scott D. Boyd,

Immunodeficiency and Autoimmune Disorders

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.