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Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans.

1993; Springer Nature; Volume: 12; Issue: 6 Linguagem: Inglês

10.1002/j.1460-2075.1993.tb05887.x

1460-2075

Shunichi Takeda, Yong‐Rui Zou, Horst Bluethmann, Daisuke Kitamura, Urs Müller, Klaus Rajewsky,

Glycosylation and Glycoproteins Research

Research Article1 June 1993free access Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans. S. Takeda S. Takeda Basel Institute for Immunology, Switzerland. Search for more papers by this author Y.R. Zou Y.R. Zou Basel Institute for Immunology, Switzerland. Search for more papers by this author H. Bluethmann H. Bluethmann Basel Institute for Immunology, Switzerland. Search for more papers by this author D. Kitamura D. Kitamura Basel Institute for Immunology, Switzerland. Search for more papers by this author U. Muller U. Muller Basel Institute for Immunology, Switzerland. Search for more papers by this author K. Rajewsky K. Rajewsky Basel Institute for Immunology, Switzerland. Search for more papers by this author S. Takeda S. Takeda Basel Institute for Immunology, Switzerland. Search for more papers by this author Y.R. Zou Y.R. Zou Basel Institute for Immunology, Switzerland. Search for more papers by this author H. Bluethmann H. Bluethmann Basel Institute for Immunology, Switzerland. Search for more papers by this author D. Kitamura D. Kitamura Basel Institute for Immunology, Switzerland. Search for more papers by this author U. Muller U. Muller Basel Institute for Immunology, Switzerland. Search for more papers by this author K. Rajewsky K. Rajewsky Basel Institute for Immunology, Switzerland. Search for more papers by this author Author Information S. Takeda1, Y.R. Zou1, H. Bluethmann1, D. Kitamura1, U. Muller1 and K. Rajewsky1 1Basel Institute for Immunology, Switzerland. The EMBO Journal (1993)12:2329-2336https://doi.org/10.1002/j.1460-2075.1993.tb05887.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Immunoglobulins (Ig) secreted from a plasma cell contain either kappa or lambda light chains, but not both. This phenomenon is termed isotypic kappa-lambda exclusion. While kappa-producing cells have their lambda chain genes in germline configuration, in most lambda-producing cells the kappa chain genes are either non-productively rearranged or deleted. To investigate the molecular mechanism for isotypic kappa-lambda exclusion, in particular the role of the Ig kappa intron enhancer, we replaced this enhancer by a neomycin resistance (neoR) gene in embryonic stem (ES) cells. B cells heterozygous for the mutation undergo V kappa-J kappa recombination exclusively in the intact Ig kappa locus but not in the mutated Ig kappa locus. Homozygous mutant mice exhibited no rearrangements in their Ig kappa loci. However, splenic B cell numbers were only slightly reduced as compared with the wild-type, and all B cells expressed lambda chain bearing surface Ig. These findings demonstrate that rearrangement in the Ig kappa locus is not essential for lambda gene rearrangement. We also generated homozygous mutant mice in which the neoR gene was inserted at the 3′ end of the Ig kappa intron enhancer. Unexpectedly, mere insertion of the neoR gene showed some suppressive effect on V kappa-J kappa recombination. However, the much more pronounced inhibition of V kappa-J kappa recombination by the replacement of the Ig kappa intron enhancer suggests that this enhancer is essential for V kappa-J kappa recombination. Previous ArticleNext Article Volume 12Issue 61 June 1993In this issue RelatedDetailsLoading ...