The change in Ig regulation from children to adults disconnects the correlation with the 3′RR hs1.2 polymorphism

BMC Immunology

Domenico Frezza⁵  Susanna Esposito²  Alessandro Plebani³  Vincenzo Giambra⁷  Marco Cattalini⁷  Pietro D’Addabbo¹  Renato Massoud⁴  Andrea Magrini⁴  Cesare Gargioli⁵  Valentina Iacoacci⁵  Laura Porretti²  Nicola Principi²  Cristina Daleno²  Eliseo Serone⁶ 

[1] Department of Biology, University of Bari, Bari, Italy;Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;Pediatrics Clinic, Department of Clinical and Experimental Sciences, Università di Brescia e Spedali Civili di Brescia, Brescia, Italy;Department of Sperimental Medicine, Policlinico Tor Vergata, Rome, Italy;Department of Biology “Enrico Calef”, University of Roma Tor Vergata, Rome, 00133, Italy;Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy;Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, BC, Canada

关键词: Aging;    Transcription factor consensus;    SP1;    NF-κB;    Immune system regulation;    Enhancer hs1.2;    Immunoglobulin heavy chain;    B cell markers;    Genotyping;   

Others  :  1089885
DOI  :  10.1186/s12865-014-0045-0

 received in 2014-01-07, accepted in 2014-09-25,  发布年份 2014

【 摘 要 】

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.

During ageing there is a physiological increase of Ig concentrations in the serum. Therefore, for this study, we hypothesized that the hs1.2 variants may impact differently the levels of secreted Ig during the growth.

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.

【 授权许可】

   
2014 Serone et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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