Department of Translational Medicine and Surgery, Catholic University of Rome, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Largo A. Gemelli, 8, Rome 00168, Italy.
Research Center, San Pietro Hospital, Fatebenefratelli, Via Cassia, 600, Rome 00189, Italy.
Gene. 2023 Apr 30;862:147254. doi: 10.1016/j.gene.2023.147254. Epub 2023 Feb 9.
Several studies in animal models have demonstrated the role of the 3' Regulatory Region (3'RR) in the B cell maturation in mammals. In healthy humans, the concentration of each class of circulating immunoglobulins (Igs) has stable but different levels, due to several control mechanisms that also involve a duplicated version of the 3'RR on the chromosome 14 (chr14). The classes' equilibrium can be altered during infections and in other pathological conditions.
We studied the concentrations of IgA, IgM, IgG classes and IgG subclasses in a cohort of 1235 people having immunoglobulin concentrations within normal range to determine the presence of any correlation between the Igs serum concentrations, age and ratio among Ig classes and IgG subclasses in healthy humans. Furthermore, we assessed the concentrations of IgE and the allelic frequency of 3'RR1 hs1.2 enhancer in a group of 115 subjects with high levels of circulating IgE due to acute exacerbation of allergic asthma and in a control group of 118 healthy subjects.
In both children and adult subjects, the concentrations of the four IgG subclasses decreased from IgG1 to IgG4. Furthermore, the 3'RR1 enhancer hs1.2 alleles contribute to the control of the IgG subclasses levels, but it does not affect the IgE levels.
The 3'RR1 controls IgG and IgE through different mechanisms, only in the IgG case involving the hs1.2 alleles. Thus, considering the IgH constant genes loci on the chromosome 14 and the multiple steps of switch that rearrange the whole region, we found that in humans the classes of Igs are modulated by mechanisms involving a complex interaction and transition between 3'RR1 and 3'RR2, also in physiological conditions.
几项动物模型研究表明，3'调控区（3'RR）在哺乳动物 B 细胞成熟中起作用。在健康人中，由于涉及染色体 14 上 3'RR 重复版本的多个控制机制，每种循环免疫球蛋白（Ig）类别的浓度具有稳定但不同的水平。在感染和其他病理条件下，类别的平衡会发生改变。
我们研究了 1235 名免疫球蛋白浓度在正常范围内的人群中 IgA、IgM、IgG 类和 IgG 亚类的浓度，以确定在健康人中，Ig 血清浓度、年龄和 Ig 类与 IgG 亚类之间的比例之间是否存在任何相关性。此外，我们评估了 115 名因过敏性哮喘急性加重而循环 IgE 水平升高的患者组和 118 名健康对照组中 IgE 的浓度和 3'RR1 hs1.2 增强子的等位基因频率。
在儿童和成年受试者中，四种 IgG 亚类的浓度从 IgG1 降低到 IgG4。此外，3'RR1 增强子 hs1.2 等位基因有助于控制 IgG 亚类的水平，但不影响 IgE 水平。
3'RR1 通过不同的机制控制 IgG 和 IgE，仅在 IgG 情况下涉及 hs1.2 等位基因。因此，考虑到染色体 14 上的 IgH 恒定基因座和重新排列整个区域的多个开关步骤，我们发现人类的 Ig 类是由涉及 3'RR1 和 3'RR2 之间复杂相互作用和转换的机制调节的，即使在生理条件下也是如此。
