Revisiting the Pig IGHC Gene Locus in Different Breeds Uncovers Nine Distinct IGHG Genes

Zhang, Ming; Li, Zhenrong; Li, Jingying; Huang, Tianhua; Peng, Gaochuang; Tang, Wenda; Yi, Guoqiang; Zhang, Lifan; Song, Yu; Liu, Tianran; Hu, Xiaoxiang; Ren, Liming; Liu, Honglin; Butler, John E.; Han, Haitang; Zhao, Yaofeng

doi:10.4049/jimmunol.1901483

Cited by 10 publications

(14 citation statements)

References 72 publications

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“…Of these, the IGHG2 subclass genes are close paralogs of IGHG1 , and the IGHG5 genes are close paralogs of IGHG4 . Importantly, the IGHG2 and IGHG5 genes are variably present and may not be present in any given porcine haplotype ( 10 ). We use this updated nomenclature throughout the remainder of this study.…”

Section: Introductionmentioning

confidence: 99%

Fc-Mediated Functions of Porcine IgG Subclasses

et al. 2022

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The pig is an important agricultural species and powerful biomedical model. We have established the pig, a large natural host animal for influenza with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies. Antibodies provide protection through neutralization and recruitment of innate effector functions through the Fc domain. However very little is known about the Fc-mediated functions of porcine IgG subclasses. We have generated 8 subclasses of two porcine monoclonal anti influenza hemagglutinin antibodies. We characterized their ability to activate complement, trigger cytotoxicity and phagocytosis by immune cells and assayed their binding to monocytes, macrophages, and natural killer cells. We show that IgG1, IgG2a, IgG2b, IgG2c and IgG4 bind well to targeted cell types and mediate complement mediated cellular cytotoxicity (CDCC), antibody dependent cellular cytotoxicity (ADCC) and antibody mediated cell phagocytosis (ADCP). IgG5b and IgG5c exhibited weak binding and variable and poor functional activity. Immune complexes of porcine IgG3 did not show any Fc-mediated functions except for binding to monocytes and macrophages and weak binding to NK cells. Interestingly, functionally similar porcine IgG subclasses clustered together in the genome. These novel findings will enhance the utility of the pig model for investigation of therapeutic antibodies.

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Section: Introductionmentioning

confidence: 99%

Fc-Mediated Functions of Porcine IgG Subclasses

et al. 2022

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“…The κ genes were conserved in most mammals and were highly similar in sequence and number, but rabbits had two κ genes in particular. Yak, mouse, rabbit, horse and pig had five Jκ genes, while goat and sheep had only three Jκ genes and one was 19 bp irregular RSS ( 20 , 25 , 46 , 47 ). Jκ1-4 was used in yak and horse VJ recombination and was similar in type and frequency of Jκ used ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cattle mainly expresses Vλ1a, Vλ1b, Jλ2 and Jλ3. Pig only Jλ2-λ2 and Jλ3-λ3 were used in recombination ( 47 , 48 ). Only the combination of Jλ1-λ1 was found in the recombination sequence for sheep ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

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Organization and Complexity of the Yak (Bos Grunniens) Immunoglobulin Loci

Zhao

Tang

et al. 2022

Front. Immunol.

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As important livestock in Qinghai-Tibet Plateau, yak provides meat and other necessities for Tibetans living. Plateau yak has resistance to diseases and stress, yet is nearly unknown in the structure and expression mechanism of yak immunoglobulin loci. Based on the published immunoglobulin genes of bovids (cattle, sheep and goat), the genomic organization of the yak immunoglobulin heavy chain (IgH) and immunoglobulin light chain (IgL) were described. The assemblage diversity of IgH, Igλ and Igκ in yak was similar to that in bovids, and contributes little to the antibody lineage compared with that in humans and mice. Somatic hypermutation (SHM) had a greater effect on immunoglobulin diversity in yak than in goat and sheep, and in addition to the complementarity-determining region (CDR), some loci in the framework region (FR) also showed high frequency mutations. CDR3 diversity showed that immunological lineages in yak were overwhelmingly generated through linkage diversity in IgH rearrangements. The emergence of new high-throughput sequencing technologies and the yak whole genome (2019) publication have greatly improved our understanding of the immune response in yaks. We had a more comprehensive analysis of yak immunoglobulin expression diversity by PE300, which avoided the disadvantage of missing low-frequency recombination in traditional Sanger sequencing. In summary, we described the schematic structure of the genomic organization of yak IgH loci and IgL loci. The analysis of immunoglobulin expression diversity showed that yak made up for the deficiency of V(D)J recombinant diversity by junctional diversity and CDR3 diversity. In addition, yak, like cattle, also had the same ultra-long IgH CDR3 (CDR3H), which provided more contribution to the diverse expression of yak immunoglobulin. These findings might provide a theoretical basis for disease resistance breeding and vaccine development in yak.

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“…Previously, the second-generation sequencing was the most commonly used method to analyze gene molecular mechanism in pig ( Liu et al, 2019b ; Tang et al, 2017 ). Recently, third-generation sequencing has been increasingly employed in studying the functional genomics and epigenetics in pig ( Beiki et al, 2019 ; Ma et al, 2021 ; Zhang et al, 2020 ). However, the AS and APA events in the pig ovary are rarely reported.…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of transcriptome complexity in pig granulosa cells by long-read isoform sequencing

Wang

et al. 2022

PeerJ

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Background In intensive and large-scale farms, abnormal estradiol levels in sows can cause reproductive disorders. The high incidence rate of reproductive disturbance will induce the elimination of productive sows in large quantities, and the poor management will bring great losses to the pig farms. The change in estradiol level has an important effect on follicular development and estrus of sows. To solve this practical problem and improve the productive capacity of sows, it is significant to further clarify the regulatory mechanism of estradiol synthesis in porcine granulosa cells (GCs). The most important function of granulosa cells is to synthesize estradiol. Thus, the studies about the complex transcriptome in porcine GCs are significant. As for precursor-messenger RNAs (pre-mRNAs), their post-transcriptional modification, such as alternative polyadenylation (APA) and alternative splicing (AS), together with long non-coding RNAs (lncRNAs), may regulate the functions of granulosa cells. However, the above modification events and their function are unclear within pig granulosa cells. Methods Combined PacBio long-read isoform sequencing (Iso-Seq) was conducted in this work for generating porcine granulosa cells’ transcriptomic data. We discovered new transcripts and possible gene loci via comparison against reference genome. Later, combined Iso-Seq data were adopted to uncover those post-transcriptional modifications such as APA or AS, together with lncRNA within porcine granulosa cells. For confirming that the Iso-Seq data were reliable, we chose four AS genes and analyzed them through RT-PCR. Results The present article illustrated that pig GCs had a complex transcriptome, which gave rise to 8,793 APA, 3,465 AS events, 703 candidate new gene loci, as well as 92 lncRNAs. The results of this study revealed the complex transcriptome in pig GCs. It provided a basis for the interpretation of the molecular mechanism in GCs.

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Revisiting the Pig IGHC Gene Locus in Different Breeds Uncovers Nine Distinct IGHG Genes

Abstract: The sequences presented in this article have been submitted to the National Center for Biotechnology Information's GenBank (http://www.ncbi.nlm.nih.gov/) under accession numbers MN735459, MN735460, and MN735461.

Cited by 10 publications

References 72 publications

Fc-Mediated Functions of Porcine IgG Subclasses

Fc-Mediated Functions of Porcine IgG Subclasses

Organization and Complexity of the Yak (Bos Grunniens) Immunoglobulin Loci

Integrative analysis of transcriptome complexity in pig granulosa cells by long-read isoform sequencing

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