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

我们使用经典免疫遗传学和分子生物学技术 兔免疫球蛋白和T细胞的遗传学研究 受体(TCR)，并研究Ig和Ig的调节表达。 淋巴样细胞发育过程中的TCR基因。 我们报告了第13次实验室观察到的VH-CH 重组(R2m)在兔体内。所有13个重组都有 发生在父本身上。R2M重组位点图3‘中的 VH基因和JH基因的5‘端，以及之前的三个位点 特征化的重组。D1d水解酶基因的R2m位点定位于3‘ 其位于含水解酶的区域的3‘端，可能位于 或者接近重复的DNA片段。可能有两个或更多 重复DNA片段内或附近的“重组热点” 在兔的含有水解酶的区域。 我们获得了DBeta2和JBeta2的完整基因组序列 与嵌合CBeta基因相关的片段存在于一些兔子中。 兔JBeta2簇有六个功能片段，一个假基因， 和JBeta2.2和JBeta2.3之间的另一个伪基因的残留物， 与在同一地点在人类身上发现的相同。JBeta2.5 兔基因片段失去剪接信号，为假基因 与人类和老鼠的同类不同。的一般组织结构 这三个物种的DBeta2-JBeta2区域的基因片段都是 在很长的DNA序列上非常保守；有 与人类的相似性比与老鼠的相似性更高。 在美国国立卫生研究院饲养的兔子产生了高水平的波长光 链缺乏c2L，只表达c7。这些兔子被展示给 产生与产物对应的序列的信使核糖核酸和蛋白质 先前发现的基因组lambda轻链基因Clambda6。 已知C2L的产生是由于Clambda5的表达。这个 C2L阴性表型反映了包括Jlambda5在内的一个区域的缺失。 Tbe c7阴性表型似乎也是由缺失引起的。

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 reported the thirteenth laboratory observation of a VH-CH recombination (R2M) in the rabbit. All thirteen recombinations have occurred in the male parent. The R2M recombination site maps 3'of the VH genes and 5'of the JH genes as did the sites of three previously characterized recombinations. The R2M site maps 3'of the D1d DH gene which is toward the 3'end of the DH-containing region and is probably in or near stretches of repetitive DNA. There may be two or more "hot-spots of recombination" within or near stretches of repetitive DNA in the DH-containing region of the rabbit. We obtained the complete genomic sequences of the DBeta2 and JBeta2 segments associated with a chimeric CBeta gene present in some rabbits. The rabbit JBeta2 cluster has six functional segments, one pseudogene, and a remnant of another pseudogene between JBeta2.2 and JBeta2.3, equivalent to the one found in man at the same location. The JBeta2.5 gene segment of rabbit has lost the splice signal and is a pseudogene unlike its counterparts in man and mouse. The general organization of the gene segments in the DBeta2-JBeta2 regions of all three species is remarkably conserved over long stretches of DNA sequence; there is higher similarity to human than mouse. 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, Clambda6. The production of c2l is known to be due to expression of Clambda5. The c2l-negative phenotype reflects deletion of a region including Jlambda5. Tbe c7-negative phenotype also appears to result from a deletion.