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

Distinct environmental exposures are associated with the maturation of antibody types in early childhood. Teaching baby B cells Antibodies are central to immune defense. B cells can generate several antibody isotypes that fulfill different functional roles, and repeated antigen exposure induces antibody somatic hypermutation. Nielsen et al. studied a longitudinal birth cohort to determine how antigen exposure early in life affects human antibody production. Somatic hypermutation increased as the children got older, and certain IGHV genes were associated with different isotypes. They found that increased pathogen exposure was associated with IgD and IgM mutations. Children with eczema or allergies had higher rates of IgE mutation. These valuable data shed light on how human B cells grow up. 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.