Venugopal G, Yang M, Luo Z, Salo D, Cheang M, Mohapatra S S
Department of Immunology, University of Manitoba, Winnipeg, Canada.
J Immunol. 1995 Dec 1;155(11):5463-70.
Allergen-induced synthesis of lgE Abs in genetically predisposed individuals constitutes the hallmark of allergic diseases; however, the molecular basis of this genetic predisposition remains unknown. T cell cytokines lL-4 and IFN-gamma reciprocally regulate lgE synthesis and are potential genetic factors governing atopy. To examine the inheritance patterns of IgE responsiveness and address the role of these cytokines as genetic predisposition factors, in this study we established a MHC-identical mouse colony comprising crosses between two inbred strains of mouse, A.SW and SJL, respectively representing high and low IgE responder phenotypes. Segregation analysis with 149 [(A.SW x SJL)F1 x SJL] backcross and 148 [(A.SW x SJL)F1 x F1]F2 mice suggested that persistent high IgE responsiveness was inherited as a simple Mendelian dominant trait under the control of a single non-MHC, autosomal gene of major effect in these strains. Since SJL lacked Tcrvb8 genes, we examined the possibility of Tcrvb8 as a candidate gene for IgE responsiveness. The results suggested association of neither the Tcrvb8 gene nor its expression with allergen-induced IgE phenotype. Furthermore, microsatellite marker and gene sequencing analyses revealed that neither of the ll4 and lfg genes was associated with IgE phenotype. Moreover, correlation studies between IgE and cytokine levels in splenocyte cultures indicated that IgE levels were moderately to poorly correlated with IL-4 and IFN-gamma levels. It is concluded that even though expression of Tcrvb8, II4, and Ifg genes may play pivotal roles in IgE regulation, these genes per se do not contribute to genetic predisposition of allergen-induced IgE hyperresponsiveness in these strains of mice.
在具有遗传易感性的个体中，变应原诱导的IgE抗体合成是过敏性疾病的标志；然而，这种遗传易感性的分子基础仍然未知。T细胞细胞因子IL-4和IFN-γ相互调节IgE合成，是控制特应性的潜在遗传因素。为了研究IgE反应性的遗传模式，并探讨这些细胞因子作为遗传易感性因素的作用，在本研究中，我们建立了一个MHC相同的小鼠群体，该群体由分别代表高IgE反应性和低IgE反应性表型的两个近交系小鼠A.SW和SJL之间的杂交组成。对149只[(A.SW×SJL)F1×SJL]回交小鼠和148只[(A.SW×SJL)F1×F1]F2小鼠进行的分离分析表明，持续的高IgE反应性在这些品系中受一个单一的非MHC常染色体主要效应基因控制，以简单孟德尔显性性状遗传。由于SJL缺乏Tcrvb8基因，我们研究了Tcrvb8作为IgE反应性候选基因的可能性。结果表明，Tcrvb8基因及其表达均与变应原诱导的IgE表型无关。此外，微卫星标记和基因测序分析显示，Il4和lfg基因均与IgE表型无关。此外，脾细胞培养物中IgE与细胞因子水平的相关性研究表明，IgE水平与IL-4和IFN-γ水平的相关性中等或较差。得出的结论是，尽管Tcrvb8、II4和Ifg基因的表达可能在IgE调节中起关键作用，但这些基因本身并不导致这些品系小鼠中变应原诱导的IgE高反应性的遗传易感性。
