TIMING ONSET OF B CELL REPERTOIRE GENERATION AND EXPORT

各种机制已被证明是负责 初级和次级淋巴细胞中抗体库的多样化 组织，详细了解分化和机制 负责广泛和V区域集中的多样化 （过度多样化）重排的免疫球蛋白基因还没有掌握。 已经观察到免疫球蛋白V基因的体细胞过度多样化 在包括小鼠、兔、反刍动物和鸡的几个物种中。 在 在反刍动物中，回肠派伊尔集合淋巴结（IPP）是主要的 B细胞库的多样化。 非常大的B细胞成员 (1X10/10 - 1X 10/11）经历发育调节，广泛的体细胞 IG基因的多样化。 尽管纸巾的易得性 这是如此大规模的B细胞多样化的网站，使其成为一个 有吸引力的制度，详细审查机制 负责这个过程，精确的动力学知识，其 缺少的开始。 此外，在时间上， 在Ipp的多样性和多样化的时候， 剧目出现在周边是不知道的。 实验 提出将采用RT-PCR和单链构象 多态性（SSCP）作为λ的体细胞多样化的测定 牛的轻链V区。 该提案有以下具体内容 目的： 1.当牛轻链V 回肠派尔集合淋巴结的区域经历多样化。 2.确定何时回肠派尔集合淋巴结的多样化 反映在外围。 这些研究将允许确定发育时间， IPP的多样化机制被激活并增加活性。 这种信息是在知情的情况下采取行动的必要前奏。 审查发起一项倡议所涉及的因素， 免疫球蛋白多样化程序在B细胞发育这一位点 和多样化。

A variety of mechanisms have been shown to be responsible for the diversification of antibody repertoires in primary and secondary lymphoid tissues, a detailed knowledge of the differentiation and mechanisms responsible for the extensive and V region-focussed diversification (hyperdiversification) of rearranged immunoglobulin genes is not in hand. Somatic hyperdiversification of immunoglobulin V genes has been observed in several species including mice, rabbits, ruminants and chickens. In ruminants, the ileal Peyer's patch (IPP) is the site of primary diversification of the B cell repertoire. Very large members of B cells (1X10/10 - 1X10/11) undergo developmentally regulated, extensive somatic diversification of Ig genes. Although the ready availability of a tissue that is the site of such massive B cell diversification make it an attractive system for the detailed examination of the mechanism responsible for this process, precise knowledge of the kinetics of its onset are lacking. Furthermore, the relationship in time between the generation of diversity in the Ipp and the time when a diversified repertoire appears in the periphery is not known. Experiments are proposed that will employ RT-PCR nd single strand conformational polymorphism (SSCP) as an assay of somatic diversification of the lambda light chain V regions of cattle. The proposal has the following specific aims: 1. Determination of the point in development when bovine light chain V regions undergo diversification in ileal Peyer's patches. 2. Determine when the diversification in ileal Peyer's patches is reflected in the periphery. These studies will allow determination of the time in development when the diversification mechanism of IPP is activated and increases in activity. Such information is a necessary prelude to the informed undertaking of an examination of the factors that are involved in the initiation of an immunoglobulin diversification program in this site of B cell development and diversification.