Abstract
Boys present with higher proportions of immature/naïve CD5+ B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3–5 days and at 8 years of age. Boys had higher proportions of CD5+ and immature/transitional CD24hiCD38hi B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+ B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.
Highlights
In children, the mortality rate in less developed countries is higher among boys than girls, they have equal access to food and medical care[1]
We have previously reported that boys present with higher proportions of circulating immature/naïve CD5+ B cells over the first 3 years of life[7] as well as with higher proportions of Tregs in cord blood and in early infancy compared to girls[4]
As boys present with lower BAFF levels in cord blood and respond with lower vaccine-induced anti-mumps and anti-rubella titers compared to girls[4,7], we examined if these factors were related to the proportions of immature/naïve B cells in non-allergic children at 8 years of life
Summary
The mortality rate in less developed countries is higher among boys than girls, they have equal access to food and medical care[1]. If cord blood testosterone or DHT levels are associated with peripheral adaptive immune maturation and the proportions of Tregs in early infancy and later in childhood among boys and girls has not been investigated. To address these gaps in knowledge, we have performed a detailed immunological follow-up of the prospective FARMFLORA birth cohort study at 8 years of age. Higher cord blood DHT, but not testosterone, levels were associated with higher proportions of immature/naïve CD5+ B cells in early infancy as well as at 8 years of age
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