Unraveling of the polymorphic Cλ2-Cλ3 amplification and the Ke+Oz- polymorphism in the human Igλ locus

Mirjam Van der Burg, Barbara H. Barendregt, Ellen J. Van Gastel-Mol, Talip Tümkaya, Anton W. Langerak, Jacques J.M. Van Dongen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalJournal of Immunology
Volume169
Issue number1
DOIs
Publication statusPublished - 1 Jul 2002

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