MECHANISM OF ALLERGIC SENSITIZATION DURING INFANCY

众所周知，除了特应性素质外，环境因素在婴儿期和幼儿期过敏性疾病的发展中也起着重要作用。特别是，婴儿早期大量接触过敏原可能会加速易感个体已有的过敏性炎症，从而导致各种过敏症状的发展。本研究是为了回答以下问题。1)血清IgE浓度和循环嗜碱性细胞FcEPSILONel表达的年龄依赖性变化。2)新生儿B细胞产生IgE的机制。重度特应性皮炎和原发性免疫缺陷疾病的病理生理机制（cd70 /CD27.3）过敏儿童血清IgE浓度呈年龄依赖性增高。出生后，FcepsilonRI在外周血嗜碱性细胞中的表达迅速增加，并有效结合1gB。1gB本身增强了FcepsilonRI的表达和1gB在嗜碱性细胞表面的结合。表面受体表达的增强依赖于蛋白质的从头合成以及通过直接1gE结合在膜上的受体蛋白的稳定。此外，在培养物中加入转染cd70的细胞后，新生儿或幼稚B细胞的IgE合成显著增强。当CD27阴性B细胞被培养时，这些效应未被观察到。这些发现，加上我们之前关于新生儿β细胞产生IgG的报道，揭示了TAU细胞衍生的细胞因子和表面配体在新生儿β细胞向浆细胞分化过程中所起的作用。最后，通过对各种具有变应性表现的免疫缺陷疾病的详细病理生理检查，揭示了免疫系统在调节变应性炎症中的重要作用。

It is known that environmental factors, in addition to atopic diathesis play important roles in the development of allergic diseases during infancy and early childhood. In particular, massive allergen exposure during early infancy may lead to development of variable allergic symptoms by accelerating pre-existing allergic inflammation in susceptible individuals. The present research was undertaken to answer following questions.1) Age-dependent changes in serum IgE concentration and FcEPSILONel expression on circulating basophils.2) Mechanism of IgE production by neonatal B cells. Augmentation of IgE synthesis through CD7O/CD27.3) Pathophysiology of severe atopic dermatitis and primary immunodeficiency disorders.Serum IgE concentration increased age-dependently in allergic children. FcepsilonRI expression on peripheral blood basophils increased rapidly after birth and it bound 1gB efficiently. 1gB itself enhanced FcepsilonRI expression and 1gB binding on basophil surface. The enhancement of surface receptor expression was dependent on de novo protein sysnthesis together with the stabilization of the receptor proteins on the membrane by direct 1gE binding.Furthermore, IgE synthesis by neonatal or naive B cells was significantly enhanced by addition of CD7O-transfected cells into the culture. These effect was not seen when CD27 negative B cells were cultured. These findings, together with our previous reports on IgG production by neonatal BETA cells, disclosed the roles played by TAU cell derived cytokines and the surface ligands in the differentiation of neonatal BETA cells into plasma cells.Finally, the detailed pathophysiological examination of various immunodeficiency disorders with allergic manifestation presented several significant roles played by immune system in regulating allergic inflammation.