Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.
Abstract: To further studies of neonatal immune responses to pathogens and vaccination, we investigated the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to those of adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult lymphoid tissue were assessed for Ig lambda light chain combinatorial, junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV) were used during fetal life than later stages and IGLV gene usage differed significantly with time, in contrast to the Ig heavy chain. Junctional diversity measured by CDR3L length was constant over time. Comparison of Ig lambda transcripts to germline revealed significant increases in nucleotide diversity over time, even during fetal life. These results suggest that the Ig lambda light chain provides an additional dimension of diversity to the equine Ig repertoire.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication Date: 2014-04-12 PubMed ID: 24726757PubMed Central: PMC4107094DOI: 10.1016/j.dci.2014.04.001Google Scholar: Lookup
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Summary
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The research paper investigates the dynamics of B lymphocyte development and immunoglobulin gene diversity in horses during different stages of development. It uncovers that lambda variable genes (IGLV) usage and nucleotide diversity increase over time, suggesting that the Ig lambda light chain provides significant diversity to the equine Ig repertoire.
B lymphocyte development and Immunoglobulin gene diversity
- The researchers have attempted to understand the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity over different developmental stages of a horse.
- Prior to this study, it had been established that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to adult Ig VDJ sequences. This study extends this previous knowledge.
- For this study, they used clones from fetal, neonatal, foal, and adult lymphoid tissue.
Ig lambda light chain combinatorial, junctional, and sequence diversity
- The researchers have focused on assessing lambda light chain combinatorial, junctional, and sequence diversity during different developmental stages.
- The study revealed that more lambda variable genes (IGLV) were used during fetal life than later stages like in neonatal, foal, or adult stage. The usage of IGLV genes significantly varies with time. This observation was in contrast to Ig heavy chain, where no such variability was observed.
- The junctional diversity measured by CDR3L length remained constant over time, irrespective of the development phase.
Increase in nucleotide diversity over time
- The study reported a significant increase in nucleotide diversity over time. This trend was seen even during the fetal life stage.
- The researchers compared Ig lambda transcripts to germline and found considerable increases in nucleotide diversity as the development progressed.
- Based on these findings, the authors proposed that the Ig lambda light chain contributes to an additional dimension of diversity to the equine Ig repertoire.
Cite This Article
APA
Tallmadge RL, Tseng CT, Felippe MJ.
(2014).
Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.
Dev Comp Immunol, 46(2), 171-179.
https://doi.org/10.1016/j.dci.2014.04.001 Publication
Researcher Affiliations
- Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: rlt8@cornell.edu.
- Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
- Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States.
MeSH Terms
- Alleles
- Amino Acid Sequence
- Animals
- B-Lymphocytes / physiology
- Fetus / metabolism
- Gene Expression Regulation, Developmental
- Horses / genetics
- Horses / metabolism
- Immunoglobulin lambda-Chains / genetics
- Immunoglobulin lambda-Chains / metabolism
- Molecular Sequence Annotation
- Molecular Sequence Data
- Sequence Homology, Amino Acid
- V(D)J Recombination
Grant Funding
- DP2 OD007216 / NIH HHS
- DP2OD007216 / NIH HHS
References
This article includes 40 references
- Almagro JC, Hernández I, Ramírez MC, Vargas-Madrazo E. Structural differences between the repertoires of mouse and human germline genes and their evolutionary implications.. Immunogenetics 1998 Apr;47(5):355-63.
- Alt F, Rosenberg N, Lewis S, Thomas E, Baltimore D. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes.. Cell 1981 Dec;27(2 Pt 1):381-90.
- Arun SS, Breuer W, Hermanns W. Immunohistochemical examination of light-chain expression (lambda/kappa ratio) in canine, feline, equine, bovine and porcine plasma cells.. Zentralbl Veterinarmed A 1996 Nov;43(9):573-6.
- Butler JE, Weber P, Sinkora M, Sun J, Ford SJ, Christenson RK. Antibody repertoire development in fetal and neonatal piglets. II. Characterization of heavy chain complementarity-determining region 3 diversity in the developing fetus.. J Immunol 2000 Dec 15;165(12):6999-7010.
- De Genst E, Saerens D, Muyldermans S, Conrath K. Antibody repertoire development in camelids.. Dev Comp Immunol 2006;30(1-2):187-98.
- Dooley H, Flajnik MF. Antibody repertoire development in cartilaginous fish.. Dev Comp Immunol 2006;30(1-2):43-56.
- Flaminio MJ, Tallmadge RL, Salles-Gomes CO, Matychak MB. Common variable immunodeficiency in horses is characterized by B cell depletion in primary and secondary lymphoid tissues.. J Clin Immunol 2009 Jan;29(1):107-16.
- Gibson D. Structural studies on normal horse immunoglobulin light chains. Detection of k-type N-terminal sequences.. Biochemistry 1974 Jun 18;13(13):2776-85.
- Hara S, Diesterbeck US, König S, Czerny CP. Transcriptional analysis of equine λ-light chains in the horse breeds Rhenish-German Coldblood and Hanoverian Warmblood.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):50-65.
- Haughton G, Lanier LL, Babcock GF, Lynes MA. Antigen-induced murine B cell lymphomas. II. Exploitation of the surface idiotype as tumor specific antigen.. J Immunol 1978 Dec;121(6):2358-62.
- Hieter PA, Korsmeyer SJ, Waldmann TA, Leder P. Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells.. Nature 1981 Apr 2;290(5805):368-72.
- Home WA, Ford JE, Gibson DM. L chain isotype regulation in horse. I. Characterization of Ig lambda genes.. J Immunol 1992 Dec 15;149(12):3927-36.
- Hood L, Gray WR, Sanders BG, Dreyer WJ. Light chain evolution. Cold Spring Harbor Symposia on Quantitative Biology 1967;32:133–146.
- Kabat EA, Wu TT. Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites.. J Immunol 1991 Sep 1;147(5):1709-19.
- Kessler S, Kim KJ, Scher I. Surface membrane kappa and lambda light chain expression on spleen cells of neonatal and maturing normal and immune-defective CBA/NB mice: the kappa:lambda ratio is constant.. J Immunol 1981 Oct;127(4):1674-8.
- Kirkham PM, Mortari F, Newton JA, Schroeder HW Jr. Immunoglobulin VH clan and family identity predicts variable domain structure and may influence antigen binding.. EMBO J 1992 Feb;11(2):603-9.
- Knott J, Bona C, Kaushik A. The primary antibody repertoire of kappa-deficient mice is characterized by non-stochastic Vlamda1 + V(H) gene family pairings and a higher degree of self-reactivity.. Scand J Immunol 1998 Jul;48(1):65-72.
- Lee J, Monson NL, Lipsky PE. The V lambda J lambda repertoire in human fetal spleen: evidence for positive selection and extensive receptor editing.. J Immunol 2000 Dec 1;165(11):6322-33.
- Lefranc MP. Nomenclature of the human immunoglobulin lambda (IGL) genes.. Exp Clin Immunogenet 2001;18(4):242-54.
- Lefranc MP, Pommié C, Ruiz M, Giudicelli V, Foulquier E, Truong L, Thouvenin-Contet V, Lefranc G. IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains.. Dev Comp Immunol 2003 Jan;27(1):55-77.
- Li YS, Hayakawa K, Hardy RR. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver.. J Exp Med 1993 Sep 1;178(3):951-60.
- Magor KE, Higgins DA, Middleton DL, Warr GW. cDNA sequence and organization of the immunoglobulin light chain gene of the duck, Anas platyrhynchos.. Dev Comp Immunol 1994 Nov-Dec;18(6):523-31.
- Near RI, Ng SC, Mudgett-Hunter M, Hudson NW, Margolies MN, Seidman JG, Haber E, Jacobson MA. Heavy and light chain contributions to antigen binding in an anti-digoxin chain recombinant antibody produced by transfection of cloned anti-digoxin antibody genes.. Mol Immunol 1990 Sep;27(9):901-9.
- Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS. Common variable immunodeficiency: a new look at an old disease.. Lancet 2008 Aug 9;372(9637):489-502.
- Ramsden DA, Wu GE. Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain.. Proc Natl Acad Sci U S A 1991 Dec 1;88(23):10721-5.
- Reynaud CA, Anquez V, Dahan A, Weill JC. A single rearrangement event generates most of the chicken immunoglobulin light chain diversity.. Cell 1985 Feb;40(2):283-91.
- Richl P, Stern U, Lipsky PE, Girschick HJ. The lambda gene immunoglobulin repertoire of human neonatal B cells.. Mol Immunol 2008 Jan;45(2):320-7.
- Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees.. Mol Biol Evol 1987 Jul;4(4):406-25.
- Schroeder HW Jr, Wang JY. Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life.. Proc Natl Acad Sci U S A 1990 Aug;87(16):6146-50.
- Schroeder HW Jr, Hillson JL, Perlmutter RM. Early restriction of the human antibody repertoire.. Science 1987 Nov 6;238(4828):791-3.
- Shiokawa S, Mortari F, Lima JO, Nuñez C, Bertrand FE 3rd, Kirkham PM, Zhu S, Dasanayake AP, Schroeder HW Jr. IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth.. J Immunol 1999 May 15;162(10):6060-70.
- Sun J, Hayward C, Shinde R, Christenson R, Ford SP, Butler JE. Antibody repertoire development in fetal and neonatal piglets. I. Four VH genes account for 80 percent of VH usage during 84 days of fetal life.. J Immunol 1998 Nov 1;161(9):5070-8.
- Sun X, Wertz N, Lager K, Sinkora M, Stepanova K, Tobin G, Butler JE. Antibody repertoire development in fetal and neonatal piglets. XXII. λ Rearrangement precedes κ rearrangement during B-cell lymphogenesis in swine.. Immunology 2012 Oct;137(2):149-59.
- Sun Y, Wang C, Wang Y, Zhang T, Ren L, Hu X, Zhang R, Meng Q, Guo Y, Fei J, Li N, Zhao Y. A comprehensive analysis of germline and expressed immunoglobulin repertoire in the horse.. Dev Comp Immunol 2010 Sep;34(9):1009-20.
- Tallmadge RL, McLaughlin K, Secor E, Ruano D, Matychak MB, Flaminio MJ. Expression of essential B cell genes and immunoglobulin isotypes suggests active development and gene recombination during equine gestation.. Dev Comp Immunol 2009 Sep;33(9):1027-38.
- Tallmadge RL, Tseng CT, King RA, Felippe MJ. Developmental progression of equine immunoglobulin heavy chain variable region diversity.. Dev Comp Immunol 2013 Sep;41(1):33-43.
- Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.. Mol Biol Evol 2011 Oct;28(10):2731-9.
- Wertz N, Vazquez J, Wells K, Sun J, Butler JE. Antibody repertoire development in fetal and neonatal piglets. XII. Three IGLV genes comprise 70% of the pre-immune repertoire and there is little junctional diversity.. Mol Immunol 2013 Oct;55(3-4):319-28.
- Lefranc MP. WHO-IUIS Nomenclature Subcommittee for immunoglobulins and T cell receptors report August 2007, 13th International Congress of Immunology, Rio de Janeiro, Brazil.. Dev Comp Immunol 2008;32(5):461-3.
- Yancopoulos GD, Desiderio SV, Paskind M, Kearney JF, Baltimore D, Alt FW. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines.. Nature 1984 Oct 25-31;311(5988):727-33.
Citations
This article has been cited 8 times.- Wibmer CK, Mashilo P. Exploiting V-Gene Bias for Rapid, High-Throughput Monoclonal Antibody Isolation from Horses. Viruses 2022 Sep 30;14(10).
- Tallmadge RL, Wang M, Sun Q, Felippe MJB. Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses. PLoS One 2018;13(9):e0202646.
- Jeon HJ, Kim K, Lee JG, Jang JY, Choi S, Fang T, Yan JJ, Han M, Jeong JC, Lee KB, Kim TJ, Ahn C, Yang J. VDJ gene usage among B-cell receptors in ABO-incompatible kidney transplantation determined by RNA-seq Transcriptomic analysis. BMC Nephrol 2017 Nov 28;18(1):340.
- Tallmadge RL, Miller SC, Parry SA, Felippe MJB. Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate. PLoS One 2017;12(5):e0177831.
- Prieto JMB, Tallmadge RL, Felippe MJB. Developmental expression of B cell molecules in equine lymphoid tissues. Vet Immunol Immunopathol 2017 Jan;183:60-71.
- Walther S, Tietze M, Czerny CP, König S, Diesterbeck US. Development of a Bioinformatics Framework for the Detection of Gene Conversion and the Analysis of Combinatorial Diversity in Immunoglobulin Heavy Chains in Four Cattle Breeds. PLoS One 2016;11(11):e0164567.
- Battista JM, Tallmadge RL, Stokol T, Felippe MJ. Hematopoiesis in the equine fetal liver suggests immune preparedness. Immunogenetics 2014 Nov;66(11):635-49.
- Qiu Y, Lei Y, Yi X, Tang X, Zhang B, Wang S, Sun X. Comparative analysis of the organization and complexity of immunoglobulin light chain loci in equids. J Anim Sci 2026 Jan 8;104.
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