The multiple shark Ig H chain genes rearrange and hypermutate autonomously.

The multiple shark Ig H chain genes rearrange and hypermutate autonomously.
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DOI:
10.4049/jimmunol.1101671
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发表时间:
2011-09-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Hsu E
Hsu E
中科院分区:
其他
文献类型:
--
作者:
Zhu C;Feng W;Weedon J;Hua P;Stefanov D;Ohta Y;Flajnik MF;Hsu E

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Sharks and skates are representatives of the earliest vertebrates with an immune system based on V(D)J rearrangement. They possess a unique Ig gene organization consisting of 15 to >50 individual IgM loci, each with one VH, two DH, one JH and one set of constant region exons. The present study attempts to understand how multiple Ig genes are regulated with respect to rearrangement initiation and to targeting during somatic hypermutation. The linkage of three single-copy IgH genes was determined, and single-cell genomic PCR studies in a neonatal animal was used to examine any relationship between relative gene position and likelihood of rearrangement. Our results show that 1–3 IgH genes are activated independently of linkage or allelic position and the data best fit with a probability model based on the hypothesis that V(D)J rearrangement occurs as a sequence of trials within the B cell. In the neonatal cell set two closely related IgH, G2A and G2B, rearranged at similar frequencies and their membrane forms were expressed at similar levels, like in other young animals. However, older animals displayed a bias in favor of the G2A isotype, which suggests that although rearrangement at G2A and G2B was randomly initiated during primary repertoire generation, the two very similar IgM sequences appear to be differentially expressed with age and exposure to antigen. We performed genomic single-cell PCR on B cells from an immunized individual to study AID targeting and found that hypermutation, like V(D)J rearrangement, occurred independently among the many shark IgH.
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发表时间: 2002-10-01
期刊: IMMUNOGENETICS
影响因子: 3.2
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发表时间: 2010-12-20
期刊: The Journal of experimental medicine
影响因子: --
作者:
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