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Light chain isotype regulation in the horse. Characterization of Ig kappa genes.
Abstract: Horse Ig kappa genes have been characterized to determine whether there may be a structural basis for the low level of kappa expression in this species. The overall organization of the J kappa-C kappa locus is remarkably similar to that of the mouse and human loci. A single C kappa exon is separated by 2.9 kb from five J kappa segments, four of which seem functional and three of which are associated with canonical recombination signal sequences. A highly conserved intron enhancer was identified upstream of the C kappa exon and a single restriction fragment in horse genomic DNA hybridized strongly with the mouse downstream kappa enhancer. Germ-line and splenic cDNA V kappa sequences were characterized and found to encode N-terminal amino acid sequences previously found by protein sequencing. Hybridization of horse genomic DNA with the horse V kappa-1 germ-line gene and a variety of mouse V kappa-region probes provided evidence for at least 20 V kappa gene segments. The results indicate that the horse possesses a functional kappa locus with a complement of variable region gene segments potentially as large as that previously found at the lambda locus although the exact numbers of functional variable region genes remains to be established for both loci. This finding suggests that the predominance of lambda-chains in horse Ig may not be simply a result of a lack of functional kappa genes or of a disproportionate number of lambda vs kappa variable region genes. The results are discussed in terms of various models of isotype regulation.
Publication Date: 1994-08-01 PubMed ID: 8027543 The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article involves the study and characterization of Ig kappa genes in horses with an aim to understand their low expression level. The study suggests that the prominence of lambda-chains in horse Ig may not be purely due to a lack of functional kappa genes or imbalance between lambda and kappa variant region genes.
Overview of the Research
- The research focuses on uncovering whether there’s a structural basis for the low level of kappa expression in horses. The scientists examined Ig kappa genes to understand this aspect.
- The researchers drew similarities between the organization of the J kappa-C kappa locus in horses, mice and humans. They found that its overall organization is remarkably alike in all three species.
In-depth Analysis of Ig Kappa Genes
- The study uncovers the intricate organization of the J kappa-C kappa locus. Here, a solitary C kappa exon is separated by 2.9kb from five J kappa segments.
- Out of these five, four seem functional and three are associated with canonical recombination signal sequences.
- The research identified a highly preserved intron enhancer upstream of the C kappa exon.
- Additionally, a single restriction fragment in horse genomic DNA showed strong hybridization with the mouse downstream kappa enhancer.
Examination of Sequence Characterizations
- The researchers have analyzed both germ-line and splenic cDNA V kappa sequences.
- These sequences were found to encode N-terminal amino acid sequences which were previously established by protein sequencing.
- Hybridization of horse genomic DNA with the horse V kappa-1 germ-line gene and various mouse V kappa-region probes gave evidence of a minimum of 20 V kappa gene segments.
Conclusions Drawn from the Research
- The results make it evident that horses have a functional kappa locus with a count of variable region gene segments potentially as large as previously discovered at the lambda locus. However, the precise numbers of these functional variable region genes remain to be established for both these loci.
- This suggests that the dominance of lambda-chains in horse Ig might not be exclusively due to a lack of functional kappa genes or uneven numbers of lambda versus kappa variable region genes.
- The results are analyzed in light of models of isotype regulation.
Cite This Article
APA
Ford JE, Home WA, Gibson DM.
(1994).
Light chain isotype regulation in the horse. Characterization of Ig kappa genes.
J Immunol, 153(3), 1099-1111.
Publication
Researcher Affiliations
- Department of Biochemistry, Sherbrooke University, Q, Canada.
MeSH Terms
- Amino Acid Sequence
- Animals
- Base Sequence
- Cloning, Molecular
- DNA, Complementary / genetics
- Gene Expression Regulation
- Genes, Immunoglobulin
- Horses / genetics
- Horses / immunology
- Humans
- Immunoglobulin kappa-Chains / genetics
- Immunoglobulin lambda-Chains
- Mice
- Molecular Sequence Data
- Restriction Mapping
- Sequence Alignment
- Sequence Homology, Amino Acid
- Sequence Homology, Nucleic Acid
Citations
This article has been cited 10 times.- Rosenfeld R, Alcalay R, Zvi A, Ben-David A, Noy-Porat T, Chitlaru T, Epstein E, Israeli O, Lazar S, Caspi N, Barnea A, Dor E, Chomsky I, Pitel S, Makdasi E, Zichel R, Mazor O. Centaur antibodies: Engineered chimeric equine-human recombinant antibodies. Front Immunol 2022;13:942317.
- Sinkora M, Stepanova K, Butler JE, Sinkora M Jr, Sinkora S, Sinkorova J. Comparative Aspects of Immunoglobulin Gene Rearrangement Arrays in Different Species. Front Immunol 2022;13:823145.
- Prieto JMB, Tallmadge RL, Felippe MJB. Developmental expression of B cell molecules in equine lymphoid tissues. Vet Immunol Immunopathol 2017 Jan;183:60-71.
- Battista JM, Tallmadge RL, Stokol T, Felippe MJ. Hematopoiesis in the equine fetal liver suggests immune preparedness. Immunogenetics 2014 Nov;66(11):635-49.
- Østevik L, Gunnes G, de Souza GA, Wien TN, Sørby R. Nasal and ocular amyloidosis in a 15-year-old horse. Acta Vet Scand 2014 Aug 27;56(1):50.
- Sun Y, Liu Z, Ren L, Wei Z, Wang P, Li N, Zhao Y. Immunoglobulin genes and diversity: what we have learned from domestic animals. J Anim Sci Biotechnol 2012 Jun 20;3(1):18.
- Das S, Nikolaidis N, Nei M. Genomic organization and evolution of immunoglobulin kappa gene enhancers and kappa deleting element in mammals. Mol Immunol 2009 Sep;46(15):3171-7.
- Wiler R, Leber R, Moore BB, VanDyk LF, Perryman LE, Meek K. Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity. Proc Natl Acad Sci U S A 1995 Dec 5;92(25):11485-9.
- Lin Y, Wang Y, Li H, Liu T, Zhang J, Guo X, Guo W, Wang Y, Liu X, Huang S, Liao H, Wang X. A platform for the rapid screening of equine immunoglobins F (ab)2 derived from single equine memory B cells able to cross-neutralize to influenza virus. Emerg Microbes Infect 2024 Dec;13(1):2396864.
- Keggan A, Freer H, Rollins A, Wagner B. Production of seven monoclonal equine immunoglobulins isotyped by multiplex analysis. Vet Immunol Immunopathol 2013 Jun 15;153(3-4):187-93.
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