Templated insertions in the rearranged chicken IgL V gene segment arise by intrachromosomal gene conversion.

Carlson, Louise; McCormack, Wayne T.; Postema, Christina E.; Humphries, E H; Thompson, Craig B.

doi:10.1101/gad.4.4.536

Cited by 78 publications

(37 citation statements)

References 27 publications

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“…Although receptor revision by gene conversion has been suggested to operate in some species (26,27), evidence that this nonreciprocal exchange can alter the reading frame in CDR3 has not been shown. Although intriguing, our recovery of nearly 100% IF rearrangements is not unique and was previously reported in chickens (9) and rabbits (28).…”

Section: Discussionmentioning

confidence: 99%

Antibody Repertoire Development in Fetal and Neonatal Piglets. VI. B Cell Lymphogenesis Occurs at Multiple Sites with Differences in the Frequency of In-frame Rearrangements

Šinkora

Sun

Šinkorová

et al. 2003

The Journal of Immunology

103

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B cell lymphogenesis in mammals occurs in various tissues during development but it is generally accepted that it operates by the same mechanism in all tissues. We show that in swine, the frequency of in-frame (IF) VDJ rearrangements differs among yolk sac, fetal liver, spleen, early thymus, bone marrow, and late thymus. All VDJ rearrangements recovered and analyzed on the 20th day of gestation (DG20) from the yolk sac were 100% IF. Those recovered at DG30 in the fetal liver were >90% IF, and this predominance of cells with apparently a single IF rearrangement continued in all organs until approximately DG45, which corresponds to the time when lymphopoiesis begins in the bone marrow. Thereafter, the proportion of IF rearrangements drops to ∼71%, i.e., the value predicted whether VDJ rearrangement is random and both chromosomes were involved. Unlike other tissues, VDJs recovered from thymus after DG50 display a pattern suggesting no selection for IF rearrangements. Regardless of differences in the proportion of IF rearrangements, we observed no significant age- or tissue-dependent changes in CDR3 diversity, N region additions, or other characteristics of fetal VDJs during ontogeny. These findings indicate there are multiple sites of B cell lymphogenesis in fetal piglets and differences in the frequency of productive VDJ rearrangements at various sites. We propose the latter to result from differential selection or a developmentally dependent change in the intrinsic mechanism of VDJ rearrangement.

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Section: Discussionmentioning

confidence: 99%

Antibody Repertoire Development in Fetal and Neonatal Piglets. VI. B Cell Lymphogenesis Occurs at Multiple Sites with Differences in the Frequency of In-frame Rearrangements

Šinkora

Sun

Šinkorová

et al. 2003

The Journal of Immunology

103

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“…In contrast to chicken Ig genes, where a pool of pseudogenes is maintained for diversification through gene conversion (12,13), it seems unlikely that the chicken CD8␣-like gene cluster is retained simply to act as a reservoir for CD8␣ gene conversion. It should be noted that in the annotated chicken genome database (GenBank locus NW_060360) and the corresponding article (14), the CD8␣-like sequences were described as genes encoding products similar to CD8␣ precursors or as five additional copies of the CD8␣ gene, respectively.…”

Section: Cd8␣ and Cd8␤ Bracket A Family Of Novel Multigenes Belongingmentioning

confidence: 99%

Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes

Liaw

Chen

Huang

et al. 2007

The Journal of Immunology

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The genomic organization of the chicken CD8α gene was investigated to determine the basis of its polymorphism. Contiguous to the CD8α gene we identified multiple DNA blocks possessing sequences homologous to CD8α. Gene conversions and recombination over evolutionary time among CD8α and these CD8α homologous genes seem to account for the observed polymorphism. Furthermore, these CD8α-like DNAs encode a distinct multigene family of immunoreceptors that have a charged or polar residue in place of the interspecies-conserved CD8α transmembrane proline residue and a short cytoplasmic tail nonhomologous to CD8α. The identification of this novel multigene family with an organization reminiscent of human killer Ig-like receptors raises compelling questions on their evolutionary relationship among immunoreceptors.

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“…Strikingly, Sale and colleagues [12 •• ] found that chicken DT40 cell subclones that were defective for various molecules involved in the repair of breaks via homologous recombination (XRCC2, XRCC3 and RAD51B) underwent significantly higher rates of somatic hypermutation than gene conversion. Considering that gene conversion, like hypermutation, requires a rearranged V(D)J (the acceptor), and that transcription or transcription-related sequences are necessary [32], it appears likely that Ig hypermutation and gene conversion share both the targeting phase and the introduction of DNA breaks. The mechanism utilized to process those breaks, however, probably differs between the two mechanisms -perhaps one (gene conversion) utilizing a pseudogene and the other (hypermutation) utilizing a sister chromatid as donors, during break repair via homologous recombination [12 •• ].…”

Section: Introduction Of Dna Lesionsmentioning

confidence: 99%

Somatic immunoglobulin hypermutation

Diaz

Casali

2002

Current Opinion in Immunology

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Immunoglobulin hypermutation provides the structural correlate for the affinity maturation of the antibody response. Characteristic modalities of this mechanism include a preponderance of pointmutations with prevalence of transitions over transversions, and the mutational hotspot RGYW sequence. Recent evidence suggests a mechanism whereby DNA-breaks induce error-prone DNA synthesis in immunoglobulin V(D)J regions by error-prone DNA polymerases. The nature of the targeting mechanism and the trans-factors effecting such breaks and their repair remain to be determined.

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Templated insertions in the rearranged chicken IgL V gene segment arise by intrachromosomal gene conversion.

Cited by 78 publications

References 27 publications

Antibody Repertoire Development in Fetal and Neonatal Piglets. VI. B Cell Lymphogenesis Occurs at Multiple Sites with Differences in the Frequency of In-frame Rearrangements

Antibody Repertoire Development in Fetal and Neonatal Piglets. VI. B Cell Lymphogenesis Occurs at Multiple Sites with Differences in the Frequency of In-frame Rearrangements

Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes

Somatic immunoglobulin hypermutation

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