Multiple immunoglobulin switch region homologies outside the heavy chain constant region locus
Multiple immunoglobulin switch region homologies outside the heavy chain constant region locus
复制标题
重链恒定区基因座外的多个免疫球蛋白开关区同源性
DOI:
10.1038/293585a0
复制
发表时间:
1981
期刊:
影响因子:
64.8
通讯作者:
Philip Leder
中科院分区:
文献类型:
--
作者:
Ilan R. Kirsch;J. Ravetch;S. Kwan;Edward E. Max;R. Ney;Philip Leder
Somatic rearrangement of gene segments enables higher organisms to generate additional genetic diversity from an essentially limited and otherwise linear genome. The only known example of this powerful mechanism in vertebrates is the immune system, in which active genes are somatically assembled from distant pieces of DNA1–3. This process operates both in V–J (light chain) or V–D–J (heavy chain) joining, to form novel variable region genes from widely separated coding segments4–9, and in heavy chain class switching, whereby assembled variable region genes are switched from one heavy chain gene to another10–14. The latter process correlates with the sequential appearance of the same V region in association with different heavy chains during B-cell development15–22. Conserved sequences adjacent to these genes may be required for the two processes4–6,23–28. In the case of the heavy chain class switch from theμto theαgene, such sequences involve 2–3-kilobase (kb) segments characterized by tandem pentanucleotide and higher-order repeats24–26,28. We have previously shown that this region has been selectively conserved in both mouse and man and therefore changed little during the 70 Myr since these species have diverged28. Using the switch segment as a hybridization probe, we now show that approximately 15 switch-like regions are present in germ-line DNA and that only one is deleted during theμ–αswitch that has occurred in the IgA-producing cell line, S107. As the heavy chain constant region locus fromμthroughεis deleted in this cell line (including all the other known heavy chain genes), we conclude that the remaining switch-like signals lie outside this region.