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

我们使用经典的免疫遗传学和分子生物学技术， 研究兔免疫球蛋白（Ig）和T细胞受体的遗传学 (Tcr)探讨IG和Tcr基因的表达调控 在淋巴细胞发育过程中。据报道， 进化上保守的IgH增强子序列和供体剪接位点， IG重链J区和IgM重链之间的内含子 恒定区（C-mu）基因。保守剪接位点的存在 人、小鼠和兔JH-C-mu内含子区的序列 基因组和利用剪接位点加工不育的C-mu 小鼠和兔发育中的B细胞表达的mRNA转录本 提示这些转录本可能在B细胞增殖过程中起调节作用。 发展 有些兔子有三种不同的Tcr C-β拷贝是不寻常的 基因.第三个基因是嵌合C（beta）2-C（beta）1基因组Tcr beta 可能由类似的不平等交换事件产生的连锁基因 与可能在NZW小鼠中缺失C（beta）1、D（beta）2和J（beta）2的基因相比。 我们在对总基因组DNA和两种DNA的Southern分析中证明了这一点。 约6和约14 kb的不同基因组克隆以及通过 测序克隆的基因组DNA。 在美国国立卫生研究院饲养的兔子， 缺乏C21且仅表达C7的链。这些兔子被证明 产生mRNA和蛋白质，其序列对应于 先前鉴定的基因组λ轻链基因，C（λ）6。的 已知c21的产生是由于C（λ）5的表达。的 c2 l阴性表型反映了包括J（λ）5的区域的缺失。 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 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.