Early expression of I epsilon, CD23 (Fc epsilon RII), IL-4R alpha, and IgEin the human fetus

Background: A major predictor of childhood atopy is the concentration of Ig E in the cord blood, but whether the source of cord blood IgE is maternal o r fetal remains unclear. Objective: We sought to determine the pattern of in situ IgE production dur ing ontogeny. Methods: Ninety-seven fetal, 142 natal, and 96 childhood samples were analy zed by using reverse transcription PCR for transcription of VDJC epsilon, I epsilon, and CD23. Thirty-eight fetal liver samples were analyzed for tile IL4RA genotype. Results: IL-4R alpha, CD23a, CD23b, and sterile I epsilon transcripts were present as early as 8 weeks' gestation. VDJC epsilon transcripts were found in second-trimester fetal liver and third-trimester cord blood, although t hey were rare. VDJCe transcripts were more common in the blood of children 9 months and older. Sequence analysis suggested that fetal VDJC epsilon was the product of selection. All fetal livers actively transcribing I epsilon , VDJC epsilon, and IL-4R alpha contained at least one copy of the atopy-as sociated IL4RA*A1902G polymorphism. Conclusion: The human fetus contains B cells that are primed to undergo IgE class switching from the earliest stages of ontogeny and can produce endog enous IgE by 20 weeks' gestation. However, IgE-producing cells are rare unt il 9 months after birth.