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L chain isotype regulation in horse. I. Characterization of Ig lambda genes.

Abstract: Analysis of 10 cDNA encoding lambda L chains of horse Ig indicated that this species may employ a relatively small number of variable region (V lambda) genes in the splenic B cell population. The V lambda sequences of all of the cDNA analyzed were closely related (> 88% identity at the nucleotide level) and were characterized by a deletion of the amino acid residue at position 3 compared with V lambda sequences so far described in other species. The 10 V lambda sequences could be grouped into three groups, V lambda 1 to V lambda 3, on the basis of a number of linked substitutions. Sequences within the groups showed the greatest divergence in the third cdr regions and at the V-J junctions. The junctional variation included amino acid substitutions on both sides of the V-J junction as well as the insertion or deletion of two to four amino acid residues. Four C lambda genes were identified in genomic blots of horse DNA, and three of these were found expressed in splenic cDNA. The fourth C lambda gene may represent a pseudogene, inasmuch as the associated J region possessed a defective heptamer joining sequence. Six of the nine possible V lambda-C lambda combinations were found in the cDNA analyzed, suggesting that genes belonging to groups V lambda 1 through V lambda 3 may rearrange to any one of three J lambda-C lambda genes. One V lambda germline gene was characterized and found to represent a distinct V lambda group (V lambda 4), not represented in the cDNA sequences analyzed. The number of germline V lambda genes was estimated to be 20 to 30, based on analysis of restriction fragments hybridizing with V lambda probes. On the basis of these data, we propose that the V lambda repertoire in horse may consist of relatively limited number of genes, of which only a few may be used at high frequency in the splenic B cell population. The results indicate that predominance of lambda-chains in horse Ig may not simply be due to the presence of a large germline V lambda gene repertoire.
Publication Date: 1992-12-15 PubMed ID: 1460283
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research explores the regulation of immunoglobulin (Ig) lambda light chains in horses, suggesting that horses utilize a limited number of variable region genes in their splenic B cells. The findings further indicate that the dominance of lambda chains in horse immunoglobulins might not be only due to the presence of a large germline variable lambda gene repertoire.

Study of Lambda Light Chains in Horses

  • The study focused on analyzing 10 cDNA encoding lambda light chains of horse immunoglobulins. The findings showed that the species may be using a relatively small number of variable region genes within the B cell population of the spleen.
  • The variable lambda sequences of all of the analyzed cDNA were found to be closely related and were marked by deletion of the amino acid residue at position 3. This characteristic sets them apart from variable lambda sequences described in other species.
  • The analyzed variable lambda sequences were grouped into three categories: variable lambda 1 to variable lambda 3, based on several linked substitutions. These sequences showed the greatest divergence in third complementarity-determining regions and at the V-J junctions.

Genes and Variations

  • Four C lambda genes were identified in the genomic blots of horse DNA, with three being expressed in splenic cDNA. The fourth gene might be a pseudogene due to its associated J region’s defective heptamer joining sequence.
  • Six out of the possible nine variable lambda-constant lambda combinations were found in the analyzed cDNA. This suggests that genes from groups variable lambda 1 through variable lambda 3 could rearrange to any one of the three J lambda-C lambda genes.

Germline Genes and Light Chain Repertoire

  • One variable lambda germline gene was characterized and found to represent a separate variable lambda group (variable lambda 4), which was not represented in the analyzed cDNA sequences.
  • The number of germline variable lambda genes was estimated to be between 20 to 30, based on the analysis of restriction fragments that hybridized with variable lambda probes.
  • Based on these findings, the researchers suggest that the variable lambda repertoire in horses consists of a relatively limited number of genes, with only a few being used frequently within the splenic B cell population.
  • The study concludes that the predominance of lambda chains in horse immunoglobulins may not be solely attributed to the presence of a large germline variable lambda gene repertoire.

Cite This Article

APA
Home WA, Ford JE, Gibson DM. (1992). L chain isotype regulation in horse. I. Characterization of Ig lambda genes. J Immunol, 149(12), 3927-3936.

Publication

ISSN: 0022-1767
NlmUniqueID: 2985117R
Country: United States
Language: English
Volume: 149
Issue: 12
Pages: 3927-3936

Researcher Affiliations

Home, W A
  • Département de Biochimie, Université de Sherbrooke, Q, Canada.
Ford, J E
    Gibson, D M

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Base Sequence
      • Blotting, Southern
      • DNA / analysis
      • DNA / isolation & purification
      • Gene Library
      • Genes, Immunoglobulin
      • Horses / genetics
      • Immunoglobulin Constant Regions / genetics
      • Immunoglobulin Joining Region / genetics
      • Immunoglobulin Variable Region / genetics
      • Immunoglobulin lambda-Chains / genetics
      • Molecular Sequence Data
      • Restriction Mapping
      • Sequence Alignment
      • Sequence Analysis, DNA

      Citations

      This article has been cited 5 times.
      1. Tallmadge RL, Tseng CT, Felippe MJ. Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse. Dev Comp Immunol 2014 Oct;46(2):171-9.
        doi: 10.1016/j.dci.2014.04.001pubmed: 24726757google scholar: lookup
      2. 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.
        doi: 10.1186/2049-1891-3-18pubmed: 22958617google scholar: lookup
      3. 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.
        doi: 10.1073/pnas.92.25.11485pubmed: 8524788google scholar: lookup
      4. Rast JP, Anderson MK, Ota T, Litman RT, Margittai M, Shamblott MJ, Litman GW. Immunoglobulin light chain class multiplicity and alternative organizational forms in early vertebrate phylogeny. Immunogenetics 1994;40(2):83-99.
        doi: 10.1007/BF00188170pubmed: 8026868google scholar: lookup
      5. 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.
        doi: 10.1016/j.vetimm.2013.02.010pubmed: 23541920google scholar: lookup