Preferential expression of IGHV and IGHD encoding antibodies with exceptionally long CDR3H and a rapid global shift in transcriptome characterizes development of bovine neonatal immunity

Pasman, Yfke; Merico, Daniele; Kaushik, Azad

doi:10.1016/j.dci.2016.08.020

Cited by 11 publications

(11 citation statements)

References 52 publications

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“…In contrast, cattle have only one functional subgroup containing ten functional IGHV genes (Niku et al 2012 ; Sinclair et al 1997 ). Functional diversity is maintained in cattle by an increased occurrence of sequence changes during recombination, a substantially increased average length of the heavy-chain complementarity-determining region (CDR) 3, and a small number of antibodies with an ultra-long CDR3 resulting from the usage of an exceptionally long IGHD gene (Berens et al 1997 ; Ma et al 2016 ; Pasman et al 2017 ; Wang et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

The antibody loci of the domestic goat (Capra hircus)

et al. 2017

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The domestic goat (Capra hircus) is an important ruminant species both as a source of antibody-based reagents for research and biomedical applications and as an economically important animal for agriculture, particularly for developing nations that maintain most of the global goat population. Characterization of the loci encoding the goat immune repertoire would be highly beneficial for both vaccine and immune reagent development. However, in goat and other species whose reference genomes were generated using short-read sequencing technologies, the immune loci are poorly assembled as a result of their repetitive nature. Our recent construction of a long-read goat genome assembly (ARS1) has facilitated characterization of all three antibody loci with high confidence and comparative analysis to cattle. We observed broad similarity of goat and cattle antibody-encoding loci but with notable differences that likely influence formation of the functional antibody repertoire. The goat heavy-chain locus is restricted to only four functional and nearly identical IGHV genes, in contrast to the ten observed in cattle. Repertoire analysis indicates that light-chain usage is more balanced in goats, with greater representation of kappa light chains (~ 20–30%) compared to that in cattle (~ 5%). The present study represents the first characterization of the goat antibody loci and will help inform future investigations of their antibody responses to disease and vaccination.Electronic supplementary materialThe online version of this article (10.1007/s00251-017-1033-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

The antibody loci of the domestic goat (Capra hircus)

et al. 2017

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“…This calculation revealed that, on day 1, Ig lambda constant region genes contribute to 92% of Ig light chain transcripts; 89% of Ig light chain transcripts on day 42; and 92% of Ig light chain transcripts in adults. The steady ratio of Ig lambda/kappa transcripts throughout equine life contrasts with the Ig light chain ratio of calves and adult cows; IGKC accounts for approximately 20% of Ig light chain transcripts in young calves but only 7% in adult cows [83]. The steady usage of Ig light chains is another instance in which the young foal immune system is equivalent to the adult horse’s immune system.…”

Section: Resultsmentioning

confidence: 99%

Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses

et al. 2018

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During the neonatal period, the ability to generate immune effector and memory responses to vaccines or pathogens is often questioned. This study was undertaken to obtain a global view of the natural differences in the expression of immune genes early in life. Our hypothesis was that transcriptome analyses of peripheral blood mononuclear cells (PBMCs) of foals (on day 1 and day 42 after birth) and adult horses would show differential gene expression profiles that characterize natural immune processes. Gene ontology enrichment analysis provided assessment of biological processes affected by age, and a list of 897 genes with ≥2 fold higher (p<0.01) expression in day 42 when compared to day 1 foal samples. Up-regulated genes included B cell and T cell receptor diversity genes; DNA replication enzymes; natural killer cell receptors; granzyme B and perforin; complement receptors; immunomodulatory receptors; cell adhesion molecules; and cytokines/chemokines and their receptors. The list of 1,383 genes that had higher (p<0.01) expression on day 1 when compared to day 42 foal samples was populated by genes with roles in innate immunity such as antimicrobial proteins; pathogen recognition receptors; cytokines/chemokines and their receptors; cell adhesion molecules; co-stimulatory molecules; and T cell receptor delta chain. Within the 742 genes with increased expression between day 42 foal and adult samples, B cell immunity was the main biological process (p = 2.4E-04). Novel data on markedly low (p<0.0001) TLR3 gene expression, and high (p≤0.01) expression of IL27, IL13RA1, IREM-1, SIRL-1, and SIRPα on day 1 compared to day 42 foal samples point out potential mechanisms of increased susceptibility to pathogens in early life. The results portray a progression from innate immune gene expression predominance early in life to adaptive immune gene expression increasing with age with a putative overlay of immune suppressing genes in the neonatal phase. These results provide insight to the unique attributes of the equine neonatal and young immune system, and offer many avenues of future investigation.

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“…While the function of these ultralong antibodies remains unclear [interestingly the proportion of ultralong antibodies is significantly higher in neonatal calves (50)], their unusual structure quickly raised the hypothesis that such antibodies could bind to antigen epitopes that were not accessible to conventionally structured immunoglobulins. For example, sites on bacterial pore proteins or proteins embedded within the complex surface coat of parasitic pathogens, which are hidden from conventional antibodies, may be potential targets.…”

Section: Genomic Organization Of Immunoglobulin Genes In the Cow And mentioning

confidence: 99%

Molecular Dissection of the Antibody Response: Opportunities and Needs for Application in Cattle

Barroso

Morrison

2020

Front. Immunol.

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Improving understanding of the bovine adaptive immune response would equip researchers to more efficiently design interventions against pathogens that impact upon food security and animal welfare. There are features of the bovine antibody response that differ substantially from other mammalian species, including the best understood models in the human and mouse. These include the ability to generate a functionally diverse immunoglobulin response despite having a fraction of the germline gene diversity that underpins this process in humans and mice, and the unique structure of a subset of immunoglobulins with "ultralong" HCDR3 domains, which are of significant interest with respect to potential therapeutics, including against human pathogens. However, a more detailed understanding of the B cell response and the production of an effective antibody response in the bovine is currently hampered by the lack of reagents for the B cell lineage. In this article we outline the current state of knowledge and capabilities with regard to B cell and antibody responses in cattle, highlight resource gaps, and summarize recent advances that have the potential to fundamentally advance our understanding of this process in the bovine host.

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Preferential expression of IGHV and IGHD encoding antibodies with exceptionally long CDR3H and a rapid global shift in transcriptome characterizes development of bovine neonatal immunity

Cited by 11 publications

References 52 publications

The antibody loci of the domestic goat (Capra hircus)

The antibody loci of the domestic goat (Capra hircus)

Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses

Molecular Dissection of the Antibody Response: Opportunities and Needs for Application in Cattle

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