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Immunogenetics

, Volume 64, Issue 5, pp 399–407 | Cite as

Organization, complexity and allelic diversity of the porcine (Sus scrofa domestica) immunoglobulin lambda locus

  • John C. Schwartz
  • Marie-Paule Lefranc
  • Michael P. Murtaugh
Original Paper

Abstract

We have characterized the organization, complexity, and expression of the porcine (Sus scrofa domestica) immunoglobulin lambda (IGL) light chain locus, which accounts for about half of antibody light chain usage in swine, yet is nearly totally unknown. Twenty-two IGL variable (IGLV) genes were identified that belong to seven subgroups. Nine genes appear to be functional. Eight possess stop codons, frameshifts, or both, and one is missing the V-EXON. Two additional genes are missing an essential cysteine residue and are classified as ORF (open reading frame). The IGLV genes are organized in two distinct clusters, a constant (C)-proximal cluster dominated by genes similar to the human IGLV3 subgroup, and a C-distal cluster dominated by genes most similar to the human IGLV8 and IGLV5 subgroups. Phylogenetic analysis reveals that the porcine IGLV8 subgroup genes have recently expanded, suggesting a particularly effective role in immunity to porcine-specific pathogens. Moreover, expression of IGLV genes is nearly exclusively restricted to the IGLV3 and IGLV8 genes. The constant locus comprises three tandem cassettes comprised of a joining (IGLJ) gene and a constant (IGLC) gene, whereas a fourth downstream IGLJ gene has no corresponding associated IGLC gene. Comparison of individual BACs generated from the same individual revealed polymorphisms in IGLC2 and several IGLV genes, indicating that allelic variation in IGLV further expands the porcine antibody light chain repertoire.

Keywords

Sus scrofa porcine light chain lambda IMGT gene rearrangement 

Notes

Acknowledgements

We would like to thank Erin Babineau for excellent technical assistance, and Dr. Jane Loveland for generous review of the manuscript. This work was supported by a grant from the U.S. National Pork Board (10-139).

References

  1. Altschul SF, Gish W, Miller W, Meyers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410PubMedGoogle Scholar
  2. Archibald AL, Bolund L, Churcher C, Fredholm M, Groenen MAM, Harlizius B, Lee KT, Milan D, Rogers J, Rothschild MF, Uenishi H, Wang J, Schook LB, the Swine Genome Sequencing Consortium (2010) Pig genome sequence – analysis and publication strategy. BMC Genom 11:438CrossRefGoogle Scholar
  3. Bergman LW, Kuehl WM (1979) Formation of an intrachain disulfide bond on nascent immunoglobulin light chains. J Biol Chem 254:8869–8876PubMedGoogle Scholar
  4. Berman JE, Nickerson KG, Pollock RR, Barth JE, Schuurman RK, Knowles DM, Chess L, Alt FW (1991) VH usage in humans: biased usage of the VH6 gene in immature B lymphoid cells. Eur J Immunol 21:1311–1314PubMedCrossRefGoogle Scholar
  5. Butler JE, Wertz N, Sun J, Wang H, Lemke C, Chardon P, Piumi F, Wells K (2005) The pre-immune variable kappa repertoire of swine is selectively generated from certain subfamilies of Vκ2 and one Jκ gene. Vet Immunol Immunop 108:127–137CrossRefGoogle Scholar
  6. Butler JE, Sun J, Wertz N, Sinkora M (2006) Antibody repertoire development in swine. Dev Comp Immunol 30:199–221PubMedCrossRefGoogle Scholar
  7. Eguchi-Ogawa T, Wertz N, Sun XZ, Puimi F, Uenishi H, Wells K, Chardon P, Tobin GJ, Butler JE (2010) Antibody repertoire development in fetal and neonatal piglets: XI. The relationship of variable heavy chain gene usage and the genomic organization of the variable heavy chain locus. J Immunol 184:3734–3742PubMedCrossRefGoogle Scholar
  8. Frippiat JP, Williams SC, Tomlinson IM, Cook GP, Cherif D, Le Paslier D, Collins JE, Dunham I, Winter G, Lefranc M-P (1995) Organization of the human immunoglobulin lambda light-chain locus on chromosome 22q11.2. Hum Mol Genet 4:983–991PubMedCrossRefGoogle Scholar
  9. Giudicelli V, Chaume D, Lefranc M-P (2005) IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res 33:D256–D261PubMedCrossRefGoogle Scholar
  10. Giudicelli V, Duroux P, Ginestoux C, Folch G, Jabado-Michaloud J, Chaume D, Lefranc M-P (2006) IMGT/LIGM-DB, the IMGT® comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic Acids Res 34:D781–D784PubMedCrossRefGoogle Scholar
  11. Gorodkin J, Cirera S, Hedegaard J, Gilchrist MJ, Panitz F, Jørgensen C, Scheibye-Knudsen K, Arvin T, Lumholdt S, Sawera M, Green T, Nielsen BJ, Havgaard JH, Rosenkilde C, Wang J, Li H, Li R, Liu B, Hu S, Dong W, Li W, Yu J, Wang J, Stærfeldt H, Wernersson R, Madsen LB, Thomsen B, Hornshøj H, Bujie Z, Wang X, Wang X, Bolund L, Brunak S, Yang H, Bendixen C, Fredholm M (2007) Porcine transcriptome analysis based on 97 non-normalized cDNA libraries and assembly of 1,021,891 expressed sequence tags. Genome Biol 8:R45PubMedCrossRefGoogle Scholar
  12. Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T, Durbin R, Eyras E, Gilbert J, Hammond M, Huminiecki L, Kasprzyk A, Lehvaslaiho H, Lijnzaad P, Melsopp C, Mongin E, Pettett R, Pocock M, Potter S, Rust A, Schmidt E, Searle S, Slater G, Smith J, Spooner W, Stabenau A, Stalker J, Stupka E, Ureta-Vidal A, Vastrik I, Clamp M (2002) The Ensembl genome database project. Nucleic Acids Res 30:38–41PubMedCrossRefGoogle Scholar
  13. Humphray SJ, Scott CE, Clark R, Marron B, Bender C, Camm N, Davis J, Jenks A, Noon A, Patel M, Sehra H, Yang F, Rogatcheva MB, Milan D, Chardon P, Rohrer G, Nonneman D, de Jong P, Meyers SN, Archibald A, Beever JE, Schook LB, Rogers J (2007) A high utility map of the pig genome. Genome Biol 8:R139PubMedCrossRefGoogle Scholar
  14. Huson DH, Richter DC, Rausch C, Dezulian T, Franz M, Rupp R (2007) Dendroscope: an interactive viewer for large phylogenetic trees. BMC Bioinform 8:460CrossRefGoogle Scholar
  15. Jung D, Giallourakis C, Mostoslavsky R, Alt FW (2006) Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol 24:541–570PubMedCrossRefGoogle Scholar
  16. Kim DR, Oettinger MA (2000) V(D)J recombination: site-specific cleavage and repair. Mol Cells 10:367–374PubMedGoogle Scholar
  17. Knight KL, Becker RS (1990) Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: implications for the generation of antibody diversity. Cell 60:963–970PubMedCrossRefGoogle Scholar
  18. Lammers BM, Beaman KD, Kim YB (1991) Sequence analysis of porcine immunoglobulin light chain cDNAs. Mol Immunol 28:877–880PubMedCrossRefGoogle Scholar
  19. Lefranc M-P (2007) WHO-IUIS Nomenclature Subcommittee for Immunoglobulins and T cell receptors report. Immunogenetics 59:899–902PubMedCrossRefGoogle Scholar
  20. Lefranc M-P (2008) WHO-IUIS Nomenclature Subcommittee for Immunoglobulins and T cell receptors report. Immunoglobulins and T cell receptors report August 2007, 13th International Congress of Immunology, Rio de Janeiro, Brazil. Dev Comp Immunol 32:461–463PubMedCrossRefGoogle Scholar
  21. Lefranc M-P, Lefranc G (2001) The immunoglobulin factsbook. Academic Press, London, pp 1–458Google Scholar
  22. Lefranc M-P, Pommié C, Ruiz M, Giudicelli V, Foulquier E, Truong L, Thouvenin-Contet V, Lefranc G (2003) IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol 27:55–77PubMedCrossRefGoogle Scholar
  23. Lefranc M-P, Pommié C, Kaas Q, Duprat E, Bosc N, Guiraudou D, Jean C, Ruiz M, Da Piédade I, Rouard M, Foulquier E, Thouvenin V, Lefranc G (2005) IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. Dev Comp Immunol 29:185–203PubMedCrossRefGoogle Scholar
  24. Lefranc M-P, Giudicelli V, Ginestoux C, Jabado-Michaloud J, Folch G, Bellahcene F, Wu Y, Gemrot E, Brochet X, Lane J, Regnier L, Ehrenmann F, Lefranc G, Duroux P (2009) IMGT®, the international ImMunoGeneTics information system®. Nucleic Acids Res 37:D1006–D1012PubMedCrossRefGoogle Scholar
  25. Malynn BA, Yancopoulos GD, Barth JE, Bona CA, Alt FW (1990) Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice. J Exp Med 171:843–859PubMedCrossRefGoogle Scholar
  26. McBlane JF, Van Gent DC, Ramsden DA, Romeo C, Cuomo CA, Gellert M, Oettinger MA (1995) Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell 83:387–395PubMedCrossRefGoogle Scholar
  27. Parslow TG, Blair DL, Murphy WJ, Granner DK (1984) Structure of the 5′ ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci U S A 81:2650–2654PubMedCrossRefGoogle Scholar
  28. Pasman Y, Saini SS, Smith E, Kaushik AK (2010) Organization and genomic complexity of bovine λ-light chain gene locus. Vet Immunol Immunop 135:306–313CrossRefGoogle Scholar
  29. Ramsden DA, Baetz KA, Wu GE (1994) Conservation of sequence in recombination signal sequence spacers. Nucleic Acids Res 22:1785–1796PubMedCrossRefGoogle Scholar
  30. Rutherford K, Parkhill J, Crook J, Horsnell T, Rice P, Rajandream MA, Barrell B (2000) Artemis: sequence visualization and annotation. Bioinformatics 16:944–945PubMedCrossRefGoogle Scholar
  31. Sanchez P, Nadel B, Cazenave PA (1991) V lambda–J lambda rearrangements are restricted within a V–J–C recombination unit in the mouse. Eur J Immunol 21:907–911PubMedCrossRefGoogle Scholar
  32. Schook LB, Beever JE, Rogers J, Humphray S, Archibald A, Chardon P, Milan D, Rohrer G, Eversole K (2005) Swine Genome Sequencing Consortium (SGSC): a strategic roadmap for sequencing the pig genome. Comp Funct Genom 6:251–255CrossRefGoogle Scholar
  33. Simpson JT, Wong K, Jackman SD, Schein JE, Jones SJ, Birol I (2009) ABySS: a parallel assembler for short read sequence data. Genome Res 19:1117–1123PubMedCrossRefGoogle Scholar
  34. Wu TT, Kabat EA (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and their myeloma light chains and their implications for antibody complementarity. J Exp Med 132:211–250PubMedCrossRefGoogle Scholar
  35. Yancopolous GD, Desiderio SV, Paskind M, Kearney JF, Baltimore D, Alt FW (1984) Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature 311:727–733CrossRefGoogle Scholar
  36. Yerle M, Lahbib-Mansais Y, Pinton P, Robic A, Goureau A, Milan D, Gellin J (1997) The cytogenetic map of the domestic pig (Sus scrofa domestica). Mamm Genom 8:592–607CrossRefGoogle Scholar
  37. Zerbino DR, Birney E (2008) Velvet: algorithms for de novo short read assembly using de bruijn graphs. Genome Res 18:821–829PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • John C. Schwartz
    • 1
  • Marie-Paule Lefranc
    • 2
  • Michael P. Murtaugh
    • 1
  1. 1.Department of Veterinary and Biomedical SciencesUniversity of MinnesotaSt. PaulUSA
  2. 2.IMGT®, the international ImMunoGeneTics information system®, Laboratoire d’ImmunoGénétique Moléculaire, Institut de Génétique Humaine UPR CNRS 1142Université Montpellier 2MontpellierFrance

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