Unraveling of the polymorphic C lambda 2-C lambda 3 amplification and the Ke+Oz- polymorphism in the human Ig lambda locus
Two polymorphisms of the human Ig(lambda) (IGL) locus have been described. The first polymorphism concerns a single, 2- or 3-fold amplification of 5.4 kb of DNA in the C(lambda)2-C(lambda)3 region. The second polymorphism is the Mcg(-)Ke(+)Oz(-) isotype, which has only been defined via serological analyses in Bence-Jones proteins of multiple myeloma patients and was assumed to be encoded by a polymorphic C(lambda)2 segment because of its high homology with the Mcg(-)Ke(-)Oz(-) C(lambda)2 isotype. It has been speculated that the Mcg(-)Ke(+)Oz(-) isotype might be encoded by a C(lambda) gene segment of the amplified C(lambda)2-C(lambda)3 region. We now unraveled both IGL gene polymorphisms. The amplification polymorphism appeared to result from a duplication, triplication, or quadruplication of a functional J-C(lambda)2 region and is likely to have originated from unequal crossing over of the J-C(lambda)2 and J-C(lambda)3 region via a 2.2-kb homologous repeat. The amplification polymorphism was found to result in the presence of one to five extra functional J-C(lambda)2 per genome regions, leading to decreased Ig(kappa):Ig(lambda) ratios on normal peripheral blood B cells. Via sequence analysis, we demonstrated that the Mcg(-)Ke(+)Oz(-) isotype is encoded by a polymorphic C(lambda)2 segment that differs from the normal C(lambda)2 gene segment at a single nucleotide position. This polymorphism was identified in only 1.5% (2 of 134) of individuals without J-C(lambda)2 amplification polymorphism and was not found in the J-C(lambda)2 amplification polymorphism of 44 individuals, indicating that the two IGL gene polymorphisms are not linked.
|Keywords||Asian Continental Ancestry Group/genetics, B-Lymphocytes/immunology/metabolism, Bence Jones Protein/genetics, Blotting, Southern, European Continental Ancestry Group/genetics, Gene Amplification/*immunology, Gene Frequency/immunology, Genetic Markers/immunology, Humans, Immunoglobulin Constant Regions/blood/chemistry/*genetics, Immunoglobulin Isotypes/blood/chemistry/*genetics, Immunoglobulin kappa-Chains/analysis/blood/genetics, Immunoglobulin lambda-Chains/blood/chemistry/*genetics, Polymorphism, Genetic/*immunology|
van der Burg, M., Barendregt, B.H., van Gastel-Mol, E.J., Tümkaya, T., Langerak, A.W., & van Dongen, J.J.M.. (2002). Unraveling of the polymorphic C lambda 2-C lambda 3 amplification and the Ke+Oz- polymorphism in the human Ig lambda locus. Journal of Immunology. Retrieved from http://hdl.handle.net/1765/9926