TY - JOUR
T1 - Unraveling of the polymorphic Cλ2-Cλ3 amplification and the Ke+Oz- polymorphism in the human Igλ locus
AU - Van der Burg, Mirjam
AU - Barendregt, Barbara H.
AU - Van Gastel-Mol, Ellen J.
AU - Tümkaya, Talip
AU - Langerak, Anton W.
AU - Van Dongen, Jacques J.M.
PY - 2002/7/1
Y1 - 2002/7/1
N2 - Two polymorphisms of the human Igλ (IGL) locus have been described. The first polymorphism concerns a single, 2- or 3-fold amplification of 5.4 kb of DNA in the Cλ2-Cλ3 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 Cλ2 segment because of its high homology with the Mcg-Ke-Oz- Cλ2 isotype. It has been speculated that the Mcg-Ke+Oz- isotype might be encoded by a Cλ gene segment of the amplified Cλ2-Cλ3 region. We now unraveled both IGL gene polymorphisms. The amplification polymorphism appeared to result from a duplication, triplication, or quadruplication of a functional J-Cλ2 region and is likely to have originated from unequal crossing over of the J-Cλ2 and J-Cλ3 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-Cλ2 per genome regions, leading to decreased IgΚ:Igλ ratios on normal peripheral blood B cells. Via sequence analysis, we demonstrated that the Mcg-Ke+Oz- isotype is encoded by a polymorphic Cλ2 segment that differs from the normal Cλ2 gene segment at a single nucleotide position. This polymorphism was identified in only 1.5% (2 of 134) of individuals without J-Cλ2 amplification polymorphism and was not found in the J-Cλ2 amplification polymorphism of 44 individuals, indicating that the two IGL gene polymorphisms are not linked.
AB - Two polymorphisms of the human Igλ (IGL) locus have been described. The first polymorphism concerns a single, 2- or 3-fold amplification of 5.4 kb of DNA in the Cλ2-Cλ3 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 Cλ2 segment because of its high homology with the Mcg-Ke-Oz- Cλ2 isotype. It has been speculated that the Mcg-Ke+Oz- isotype might be encoded by a Cλ gene segment of the amplified Cλ2-Cλ3 region. We now unraveled both IGL gene polymorphisms. The amplification polymorphism appeared to result from a duplication, triplication, or quadruplication of a functional J-Cλ2 region and is likely to have originated from unequal crossing over of the J-Cλ2 and J-Cλ3 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-Cλ2 per genome regions, leading to decreased IgΚ:Igλ ratios on normal peripheral blood B cells. Via sequence analysis, we demonstrated that the Mcg-Ke+Oz- isotype is encoded by a polymorphic Cλ2 segment that differs from the normal Cλ2 gene segment at a single nucleotide position. This polymorphism was identified in only 1.5% (2 of 134) of individuals without J-Cλ2 amplification polymorphism and was not found in the J-Cλ2 amplification polymorphism of 44 individuals, indicating that the two IGL gene polymorphisms are not linked.
UR - http://www.scopus.com/inward/record.url?scp=0036644068&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.169.1.271
DO - 10.4049/jimmunol.169.1.271
M3 - Article
C2 - 12077254
AN - SCOPUS:0036644068
SN - 0022-1767
VL - 169
SP - 271
EP - 276
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -