Sheehan K M, Mainville C A, Willert S, Brodeur P H
Immunology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.
J Immunol. 1993 Nov 15;151(10):5364-75.
The utilization of VH gene families is severely biased during fetal development, such that D-region proximal VH genes are overrepresented. After birth the VH repertoire becomes more equally representative of the total inherited set of functional VH genes. To investigate the extent of this normalization process, we have determined the relative utilization of individual VH exons in the pre-immune repertoire of adult BALB/c spleen cells. Large samples of IgM heavy chain transcripts from polyclonally activated B cells were captured in a cDNA phage library and screened by hybridization using highly specific oligonucleotide probes. These studies revealed that the utilization of particular VH exons can differ by an order of magnitude. Significantly, the VH genes most under-represented in the pre-immune repertoire are located in the region of the Igh locus most distal to the DjhCh region. We suggest that the chromosomal position of a particular VH gene may influence its utilization and that the normalization of the adult repertoire is incomplete.
在胎儿发育过程中，VH基因家族的利用存在严重偏差，使得D区近端VH基因过度表达。出生后，VH基因库更能平等地代表功能性VH基因的全部遗传集合。为了研究这种正常化过程的程度，我们确定了成年BALB/c脾细胞免疫前基因库中单个VH外显子的相对利用率。来自多克隆激活B细胞的大量IgM重链转录本在cDNA噬菌体文库中捕获，并使用高度特异性寡核苷酸探针通过杂交进行筛选。这些研究表明，特定VH外显子的利用率可能相差一个数量级。值得注意的是，在免疫前基因库中代表性最低的VH基因位于Igh基因座中最远离DjhCh区域的区域。我们认为特定VH基因的染色体位置可能影响其利用率，并且成年基因库的正常化是不完全的。
