Sanz I, Wang S S, Meneses G, Fischbach M
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
J Immunol. 1994 Apr 15;152(8):3958-69.
Antibody VDJ recombination is ensured by evolutionarily conserved recombination signals (RS). The 12/23 rule postulates that only gene segments with asymmetrically spaced RS recombine with one another. Two unusually long D genes (170 bp) with irregular RS (DIR) have been reported in humans and have been postulated to participate actively in VDJ recombination, thus frequently contributing to the Ab heavy chain third hypervariable region (CDR3). However, the limited sequence information retained in the CDR3 along with significant sequence diversity has precluded an accurate assessment of the actual role and genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle in terms of their precise mechanism of recombination because they possess multiple and imperfect RS, often located up to 30 bp away from the recombining fragment within the DIR coding region. Here we present conclusive evidence for the existence of additional human germ-line DIR genes and preliminary evidence that suggests the absence of DIR-like sequences in nonprimate animals. We also show that DIR genes are under the transcriptional control of VH-independent promoters and have the potential to encode a D mu protein of 105 amino acids. Finally, DIR genes seem at least in early fetal life to recombine preferentially through the conventional 3' RS.
抗体VDJ重组由进化上保守的重组信号（RS）确保。12/23规则假定只有具有不对称间隔RS的基因片段才能彼此重组。在人类中已报道了两个具有不规则RS（DIR）的异常长的D基因（170 bp），并假定它们积极参与VDJ重组，从而频繁地对抗体重链第三高变区（CDR3）有贡献。然而，CDR3中保留的有限序列信息以及显著的序列多样性妨碍了对DIR基因实际作用和基因组多样性的准确评估。此外，DIR基因在其精确的重组机制方面构成了一个有趣的谜题，因为它们拥有多个且不完美的RS，这些RS通常位于DIR编码区内离重组片段达30 bp远的位置。在此，我们提供了人类额外种系DIR基因存在的确凿证据以及非灵长类动物中不存在DIR样序列的初步证据。我们还表明，DIR基因受不依赖VH的启动子转录控制，并且有潜力编码一个含105个氨基酸的Dμ蛋白。最后，DIR基因似乎至少在胎儿早期优先通过传统的3' RS进行重组。
