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

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

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.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging
  • Antibodies / genetics
  • Antigens / immunology
  • B-Lymphocytes / immunology
  • Carbanilides
  • Child, Preschool
  • Clone Cells
  • Communicable Diseases / immunology*
  • Eczema / immunology
  • Environment*
  • Family Characteristics
  • Female
  • Humans
  • Hypersensitivity / immunology
  • Immunoglobulin Class Switching
  • Immunoglobulin E / metabolism
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Infant
  • Male
  • Receptors, Antigen, B-Cell / metabolism*
  • Somatic Hypermutation, Immunoglobulin
  • Vaccines / immunology

Substances

  • Antibodies
  • Antigens
  • Carbanilides
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell
  • Vaccines
  • Immunoglobulin E
  • triclocarban