IG GENETICS--ONTOGENY AND DIFFERENTIATION OF CELLS OF THE RABBIT IMMUNE SYSTEM

IG遗传学--兔免疫系统细胞的个体发育和分化

• 批准号: 3809535
• 负责人: R G MAGE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3809535
• 关键词: B lymphocyte; RNA splicing; T cell receptor; T lymphocyte; cell differentiation; developmental genetics; gene deletion mutation; gene expression; genetic manipulation; genetic regulation; genetic strain; immunoglobulin genes; immunoregulation; laboratory rabbit; leukocyte activation /transformation; messenger RNA; mutant; natural gene amplification; nucleic acid hybridization

We use techniques of classical immunogenetics and of molecular biology to study the genetics of rabbit immunoglobulins (Igs) and T cell receptors (Tcr) and to investigate the regulated expression of Ig and Tcr genes during lymphoid cell development. We have reported that there are evolutionarily conserved IgH enhancer sequences and a donor splice site in the intron between the Ig heavy chain J-region and the IgM heavy chain constant region (C-mu) genes. The presence of the conserved splice site sequences in the JH-C-mu intron region of the human, mouse and rabbit genomes and the utilization of the splice sites to process sterile C-mu mRNA transcripts expressed by developing B cells of mice and rabbits suggests that these transcripts may play a regulatory role during B-cell development. Some rabbits are unusual in having three different copies of Tcr C-beta genes. The third gene is a chimeric C(beta)2-C(beta)1 genomic Tcr beta chain gene that may have arisen by an unequal crossing over event analogous to that which may have deleted C(beta)l, D(beta)2 and J(beta)2 in NZW mice. We demonstrated this in Southern analyses of both total genomic DNA and two different genomic clones of about 6 and about 14 kb as well as by sequencing cloned genomic DNA. Rabbits were bred at the NIH to produce elevated levels of lambda light chains lacking c2l and expressing only c7. These rabbits were shown to produce mRNA and proteins with sequences corresponding to the products of a previously identified genomic lambda light chain gene, C(lambda)6. The production of c2l is known to be due to expression of C(lambda)5. The c2l-negative phenotype reflects deletion of a region including J(lambda)5. The c7-negative phenotype also appears to result from a deletion.

我们使用经典免疫遗传学和分子生物学技术 研究兔免疫球蛋白（IGS）和T细胞受体的遗传学 （TCR）并研究Ig和TCR基因的调节表达 在淋巴样细胞发育过程中。我们报告说有 进化保守的IGH增强子序列和供体剪接位点 IG重链J-Region和IgM重链之间的内含子 恒定区域（C-MU）基因。保守剪接位点的存在 人，小鼠和兔子的JH-C-MU内含子区域中的序列 基因组和剪接位点的利用来处理无菌C-MU 由小鼠和兔子的B细胞表达的mRNA转录本 表明这些成绩单可能在B细胞期间起调节作用 发展。 有些兔子在拥有三个不同的tcr c-beta方面是不寻常的 基因。第三个基因是嵌合C（beta）2-C（beta）1基因组TCRβ 可能因事件类似事件而产生的链基因 在NZW小鼠中可能删除了C（beta）L，D（beta）2和J（beta）2的内容。 我们在总基因组DNA和两个分析中证明了这一点 不同的基因组克隆约为6和约14 kb，以及 测序克隆的基因组DNA。 兔子在NIH上繁殖以产生升高的兰伯达光 缺乏C2L并仅表示C7的链。这些兔子被证明 产生mRNA和蛋白质，序列与A的产物相对应 先前鉴定的基因组Lambda轻链基因C（Lambda）6。这 C2L的产生归因于C（Lambda）5的表达。这 C2L阴性表型反映了包括J（Lambda）5的区域的缺失。 C7阴性表型也似乎是由缺失引起的。