IN VIVO REGULATION OF IGE PRODUCTION
IN VIVO REGULATION OF IGE PRODUCTION
批准号:
6285616
负责人:
Juan Lafaille
金额:
$23.38万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-01-01 至 2005-12-31
关键词:
B cell receptor B lymphocyte antibody formation cell cell interaction gene expression gene rearrangement genetically modified animals helper T lymphocyte immunoglobulin A immunoglobulin E immunoglobulin G immunoglobulin genes interferon gamma interleukin 4 interleukin 5 laboratory mouse microorganism hemagglutinin receptor binding respiratory hypersensitivity
中文摘要
描述:(改编自《调查者摘要》):免疫加剧
对环境空气传播的非致病抗原(过敏原)的反应是一种
哮喘发生发展的主要因素。过敏性反应
呼吸道是由肥大细胞上IgE分子的抗原交联物触发的,
导致平滑肌活性介质的脱颗粒和释放
收缩和发炎。事实证明,最重要的因素之一
过敏反应的决定因素是T辅助淋巴细胞的刺激
2型(Th2),通过同源T/B相互作用和IL-4分泌
介导B淋巴细胞向免疫球蛋白E的产生,并通过分泌
IL-5调节嗜酸性粒细胞的募集、分化和激活。
这方面的应用主要集中在体内对IgE产生的调节。vbl.使用
同源重组,我们插入了一个重排的VDJ重链基因
以及流感病毒的重排主播轻链基因
将血凝素特异性B细胞杂交瘤导入小鼠基因组。B细胞来源
这些小鼠维持着控制体细胞生长的生理因素
高突变和同型转换,但与正常小鼠相反,
抗原特异性细胞很容易被跟踪。这些老鼠将使我们能够
评估促进同种异型的不同信号的相对重要性
改用IgE,从而定义了产生IgE的方式
被阻止的或被削弱的。具体来说,我们会:
1)确定有利于产生抗原特异性IgE的条件
活体内;
2)评估B细胞受体对其抗原的亲和力的重要性
关于免疫球蛋白类开关;
3)确定非IgE抗体是否表达相同的抗原特异性
IgE抗体可以调节呼吸道的反应,并且
4)确定T细胞是否参与了IgE的下调
回应。
我们相信,拟议的实验将加强我们对
调节IgE的产生以响应抗原,并将开辟新的途径
用于治疗特应性疾病。
英文摘要
DESCRIPTION: (Adapted from the Investigator's abstract): Exacerbated immune
responses to environmental airborne non-pathogenic antigens (allergens) are one
of the main factors for the development of asthma. Allergic reactions in the
airways are triggered by antigen crosslinking of IgE molecules on mast cells,
leading to degranulation and release of active mediators of smooth muscle
constriction and inflammation. It has been shown that one of the essential
determinant of allergic responses is the stimulation of T helper lymphocytes of
the type 2 (Th2), which, through cognate T/B interaction and IL-4 secretion
mediate B lymphocyte switch to IgE production, and through the secretion of
IL-5, regulate the recruitment, differentiation and activation of eosinophils.
This application is focused on the in vivo regulation of IgE production. Using
homologous recombination, we have inserted a rearranged VDJ heavy chain gene as
well as a rearranged VJ light chain gene from an influenza
hemagglutinin-specific B cell hybridoma into the genome of mice. B cells from
these mice maintain the physiological elements controlling somatic
hypermutation and isotype switching, but, contrary to normal mice, the fate of
antigen-specific cells can be easily followed. These mice will enable us to
assess the relative importance of the different signals which promote isotype
switching to IgE, thus defining ways in which the generation of IgE could be
prevented or downregulated. Specifically, we will:
1) determine the conditions which favor the generation of antigen-specific IgE
in vivo;
2) assess the importance of the affinity of the B cell receptor for its antigen
on immunoglobulin class switch;
3) determine whether non-IgE antibodies expressing the same antigen-specificity
of IgE antibodies can modulate the response in the airways, and
4) determine whether T cells are involved in the downregulation of IgE
responses.
We believe that the proposed experiments will enhance our knowledge on the
regulation of IgE production in response to antigen, and will open new avenues
for therapy of atopic disease.
期刊论文(0)
专著(0)
科研奖励(0)
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