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


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.

Type Journal
ISBN 1946-6242 (Electronic) 1946-6234 (Linking)
Authors Nielsen, S. C. A.; Roskin, K. M.; Jackson, K. J. L.; Joshi, S. A.; Nejad, P.; Lee, J. Y.; Wagar, L. E.; Pham, T. D.; Hoh, R. A.; Nguyen, K. D.; Tsunemoto, H. Y.; Patel, S. B.; Tibshirani, R.; Ley, C.; Davis, M. M.; Parsonnet, J.; Boyd, S. D.
Responsible Garvan Author Dr Katherine Jackson
Publisher Name Science Translational Medicine
Published Date 2019-02-27
Published Volume 11
Published Issue 481
Status Published in-print
DOI 10.1126/scitranslmed.aat2004
URL link to publisher's version