Dataset Information

Developmental progression of equine immunoglobulin heavy chain variable region diversity.

ABSTRACT: Humoral immunity is a critical component of the immune system that is established during fetal life and expands upon exposure to pathogens. The extensive humoral immune response repertoire is generated in large part via immunoglobulin (Ig) heavy chain variable region diversity. The horse is a useful model to study the development of humoral diversity because the placenta does not transfer maternal antibodies; therefore, Igs detected in the fetus and pre-suckle neonate were generated in utero. The goal of this study was to compare the equine fetal Ig VDJ repertoire to that of neonatal, foal, and adult horse stages of life. We found similar profiles of IGHV, IGHD, and IGHJ gene usage throughout life, including predominant usage of IGHV2S3, IGHD18S1, and IGHJ1S5. CDR3H lengths were also comparable throughout life. Unexpectedly, Ig sequence diversity significantly increased between the fetal and neonatal age, and, as expected, between the foal and adult age.

SUBMITTER: Tallmadge RL

PROVIDER: S-EPMC3672396 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Developmental progression of equine immunoglobulin heavy chain variable region diversity.

Tallmadge Rebecca L RL Tseng Chia T CT King Rebecca A RA Felippe M Julia B MJ

Developmental and comparative immunology 20130406 1

Humoral immunity is a critical component of the immune system that is established during fetal life and expands upon exposure to pathogens. The extensive humoral immune response repertoire is generated in large part via immunoglobulin (Ig) heavy chain variable region diversity. The horse is a useful model to study the development of humoral diversity because the placenta does not transfer maternal antibodies; therefore, Igs detected in the fetus and pre-suckle neonate were generated in utero. Th ...[more]

PMID: 23567345

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Project description:BackgroundSegmental duplication and deletion were implicated for a region containing the human immunoglobulin heavy chain variable (IGHV) gene segments, 1.9III/hv3005 (possible allelic variants of IGHV3-30) and hv3019b9 (a possible allelic variant of IGHV3-33). However, very little is known about the ranges of the duplication and the polymorphic region. This is mainly because of the difficulty associated with distinguishing between allelic and paralogous sequences in the IGHV region containing extensive repetitive sequences. Inability to separate the two parental haploid genomes in the subjects is another serious barrier. To address these issues, unique DNA sequence tags evenly distributed within and flanking the duplicated region implicated by the previous studies were selected. The selected tags in single sperm from six unrelated healthy donors were amplified by multiplex PCR followed by microarray detection. In this way, individual haplotypes of different parental origins in the sperm donors could be analyzed separately and precisely. The identified polymorphic region was further analyzed at the nucleotide sequence level using sequences from the three human genomic sequence assemblies in the database.ResultsA large polymorphic region was identified using the selected sequence tags. Four of the 12 haplotypes were shown to contain consecutively undetectable tags spanning in a variable range. Detailed analysis of sequences from the genomic sequence assemblies revealed two large duplicate sequence blocks of 24,696 bp and 24,387 bp, respectively, and an incomplete copy of 961 bp in this region. It contains up to 13 IGHV gene segments depending on haplotypes. A polymorphic region was found to be located within the duplicated blocks. The variants of this polymorphism unusually diverged at the nucleotide sequence level and in IGHV gene segment number, composition and organization, indicating a limited selection pressure in general. However, the divergence level within the gene segments is significantly different from that in the intergenic regions indicating that these regions may have been subject to different selection pressures and that the IGHV gene segments in this region are functionally important.ConclusionsNon-reciprocal genetic rearrangements associated with large duplicate sequence blocks could substantially contribute to the IGHV region diversity. Since the resulting polymorphisms may affect the number, composition and organization of the gene segments in this region, it may have significant impact on the function of the IGHV gene segment repertoire, antibody diversity, and therefore, the immune system. Because one of the gene segments, 3-30 (1.9III), is associated with autoimmune diseases, it could be of diagnostic significance to learn about the variants in the haplotypes by using the multiplex haplotype analysis system used in the present study with DNA sequence tags specific for the variants of all gene segments in this region.

Dataset Information

Developmental progression of equine immunoglobulin heavy chain variable region diversity.

Publications

Developmental progression of equine immunoglobulin heavy chain variable region diversity.

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