Early expression of iepsilon, CD23 (FcepsilonRII), IL-4Ralpha, and IgE in the human fetus.
BACKGROUND
A major predictor of childhood atopy is the concentration of IgE in the cord blood, but whether the source of cord blood IgE is maternal or fetal remains unclear.


OBJECTIVE
We sought to determine the pattern of in situ IgE production during ontogeny.


METHODS
Ninety-seven fetal, 142 natal, and 96 childhood samples were analyzed by using reverse transcription PCR for transcription of VDJCepsilon, Iepsilon, and CD23. Thirty-eight fetal liver samples were analyzed for the IL4RA genotype.


RESULTS
IL-4Ralpha, CD23a, CD23b, and sterile Iepsilon transcripts were present as early as 8 weeks' gestation. VDJCepsilon transcripts were found in second-trimester fetal liver and third-trimester cord blood, although they were rare. VDJCepsilon transcripts were more common in the blood of children 9 months and older. Sequence analysis suggested that fetal VDJCepsilon was the product of selection. All fetal livers actively transcribing Iepsilon, VDJCepsilon, and IL-4Ralpha contained at least one copy of the atopy-associated IL4RA*A1902G polymorphism.


CONCLUSIONS
The human fetus contains B cells that are primed to undergo IgE class switching from the earliest stages of ontogeny and can produce endogenous IgE by 20 weeks' gestation. However, IgE-producing cells are rare until 9 months after birth.
Lima
J O
JO
Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, AL, USA.
Zhang
L
L
Atkinson
T P
TP
Philips
J
J
Dasanayake
A P
AP
Schroeder
H W
HW
D000328:Adult; D000483:Alleles; D002460:Cell Line; D005312:Fetal Blood; D005333:Fetus / Q000276:immunology*; D015870:Gene Expression; D005865:Gestational Age; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007073:Immunoglobulin E / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007223:Infant; D008099:Liver / Q000196:embryology / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D013997:Time Factors
D007127:Immunoglobulin Constant Regions; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007139:Immunoglobulin epsilon-Chains; D007148:Immunoglobulin mu-Chains; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D007073:Immunoglobulin E