UNUSUAL PATHS AND SITES OF V REGION DIVERSIFICATION

V区多元化的不寻常路径和地点

• 批准号: 2604509
• 负责人: Richard A Goldsby
• 金额: $ 10.73万
• 依托单位: AMHERST COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2604509
• 关键词: antibody formation; cow; gene expression; gene rearrangement; immunoglobulin genes

DESCRIPTION (Adapted from the Investigator's Abstract): More than one anatomical site appears to be involved in the diversification of the bovine primary heavy chain repertoire. It has been found that although the ileal Peyer's patch (IPP) is a site of diversification in newborn and older calves, during early fetal development, spleen, but not ileum, harbors a diverse collection of heavy chain sequences. Although in cattle and sheep, immunoglobulin is not expressed in bone marrow of newborn and older calves, heavy chain expression can be readily demonstrated in early fetal bone marrow. There is also a dramatic variation in the CDR3 length noted in cattle, suggesting another unusual feature of heavy chain diversification. A knowledge of the germline is necessary to determine whether D segments of extremely variable length or the rearrangement of multiple D segments underlies CDR3 length variation. Additionally, germline data is necessary to determine whether untemplated somatic hypermutation, gene conversion or a combination of both are significant factors in generating the VH diversity found in follicles of the IPP or in early fetal spleen. To determine the mechanisms underlying bovine heavy chain diversification, the following specific aims will be pursued: 1) Determine the sites of diversification of the heavy chain primary repertoire in cattle; 2) Obtain germline heavy chain VH, DH, and JH genes; and 3) Examine the mechanism of heavy chain diversification in cattle.

描述（改编自研究者摘要）：不止一个 解剖部位似乎参与了牛的多样化 初级重链库。 已经发现，虽然回肠 派尔集合淋巴结（IPP）是新生儿和老年人的多样化部位 小牛，在胎儿发育早期，脾脏，但不是回肠， 重链序列的多样性集合。 虽然在牛和羊， 免疫球蛋白在新生和年老小牛的骨髓中不表达， 在早期胎儿骨中可以容易地证实重链表达 骨髓 在CDR 3长度中也存在显著的变化，如图1所示。 牛，这表明重链多样化的另一个不寻常的特征。 生殖系的知识是必要的，以确定是否D片段的 长度变化极大或多个D片段重排 是CDR 3长度变异的基础。 此外，生殖系数据是必要的 以确定是否无模板的体细胞超突变，基因转换或 两者的组合是产生VH多样性的重要因素 在IPP的滤泡或早期胎儿脾脏中发现。 确定 牛重链多样化的潜在机制， 具体目标将追求：1）确定多样化的网站， 牛中重链主要库; 2）获得生殖系重链 VH、DH和JH基因;和3）检查重链的机制 牛的多样化。