The change in Ig regulation from children to adults disconnects the correlation with the 3'RR hs1.2 polymorphism.
BACKGROUND
In the immune system, the serum levels of immunoglobulin (Ig) increase gradually during ageing. Through B cell development, the Ig heavy chain expression is modulated by a regulatory region at the 3' of the constant alpha gene (3'RR), in single copy in rodents and, due to a large duplication, in two copies in apes. The human 3'RR1 and 3'RR2 are both characterized by three enhancers, the central of which, namely hs1.2, is highly polymorphic. Human hs1.2 has four different variants with unique binding sites for transcription factors (e.g. NF-kB and SP1) and shows variable allelic frequencies in populations with immune disorders. In previous works, we have reported that in several autoimmune diseases the *2 allele of hs1.2 is genetically associated to high level of IgM in peripheral blood. In subjects with altered levels of circulating Ig, an increased level was associated to *2 allele of hs1.2 and low levels corresponded to high frequency of *1 allele.


RESULTS
We have correlated the allelic frequencies of hs1.2 with IgM, IgG and IgA serum concentrations in two cohorts of healthy people of different age and after three years follow-up in children homozygous for the allele. Here we show that when the expression levels of Ig in children are low and medium, the frequencies of *1 and *2 alleles are the same. Instead, when the Ig expression levels are high, there is a significantly higher frequency of the allele *2. The follow-up of children homozygous for *1 and *2 alleles showed that the increase or decrease of circulating Ig was not dependent on the number of circulating mature B cells.


CONCLUSIONS
These data support the idea that under physiologic condition there is a switch of regulative pathways involved in the maturation of Ig during ageing. This mechanism is evidenced by hs1.2 variants that in children but not in adults participate to Ig production, coordinating the three class levels.
Eliseo
E
Serone
Cristina
C
Daleno
Nicola
N
Principi
Laura
L
Porretti
Valentina
V
Iacoacci
Cesare
C
Gargioli
Andrea
A
Magrini
Renato
R
Massoud
Pietro
P
D'Addabbo
Marco
M
Cattalini
Vincenzo
V
Giambra
Alessandro
A
Plebani
Susanna
S
Esposito
Domenico
D
Frezza
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000097:blood / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic
D007137:Immunoglobulin alpha-Chains