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

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.