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Molecular characterization of a human V lambda VIII germline gene
L Y Ch'ang1, M Schell, C Ringelberg
1Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920.
Molecular Immunology
|January 1, 1995
Summary
Researchers identified a human V lambda VIII germline gene, IGLV8A1, crucial for autoantibody production. This gene
Area of Science:
- Immunogenetics
- Molecular Biology
- Protein Chemistry
Background:
- Human lambda light chains, specifically the V lambda VIII subgroup, possess unique characteristics.
- These V lambda VIII proteins are associated with specific autoantibodies, such as rheumatoid factors (RFs).
Purpose of the Study:
- To clone and characterize the germline gene encoding the human V lambda VIII subgroup.
- To investigate the structural and evolutionary significance of the V lambda VIII subgroup.
Main Methods:
- Polymerase chain reaction (PCR) was used to generate a probe for screening a human placental DNA library.
- A V lambda VIII-encoding germline gene, IGLV8A1, was cloned.
- Expressed products were analyzed using cDNA from monoclonal B-cell populations.
Main Results:
- The cloned gene, IGLV8A1, contains functional gene elements.
- V lambda VIII light chains exhibit distinct structural features, including unique residues in framework region 1 (FR1) and an elongated second complementarity-determining region (CDR2).
- IGLV8A1 shows homology to rabbit and mouse V lambda genes, suggesting evolutionary conservation.
Conclusions:
- The V lambda VIII subgroup is evolutionarily conserved, indicating functional importance.
- The elongated CDR2 region in V lambda VIII light chains likely induces novel structural effects, contributing to their biological significance.