Immunoglobulin Kappa Chain

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Klaus Rajewsky - One of the best experts on this subject based on the ideXlab platform.

  • development of Immunoglobulin lambda Chain ndash positive b cells but not editing of Immunoglobulin Kappa Chain depends on nf Kappa b signals
    Nature Immunology, 2009
    Co-Authors: Emmanuel Derudder, Emily J Cadera, Jing Wang, Manolis Pasparakis, Mark S Schlissel, Marc Schmidtsupprian, Christoph J Vahl, Klaus Rajewsky
    Abstract:

    By genetically ablating IB kinase (IKK)-mediated activation of the transcription factor NF-B in the B cell lineage and by analyzing a mouse mutant in which Immunoglobulin -Chain–positive B cells are generated in the absence of rearrangements in the locus encoding Immunoglobulin -Chain, we define here two distinct, consecutive phases of early B cell development that differ in their dependence on IKK-mediated NF-B signaling. During the first phase, in which NF-B signaling is dispensable, predominantly -Chain-positive B cells are generated, which undergo efficient receptor editing. In the second phase, predominantly -Chain-positive B cells are generated whose development is ontogenetically timed to occur after rearrangements of the locus encoding -Chain. This second phase of development is dependent on NF-B signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2.

  • development of Immunoglobulin lambda Chain positive b cells but not editing of Immunoglobulin Kappa Chain depends on nf Kappa b signals
    Nature Immunology, 2009
    Co-Authors: Emmanuel Derudder, Emily J Cadera, J C Vahl, Jing Wang, Manolis Pasparakis, Mark S Schlissel, Marc Schmidtsupprian, Klaus Rajewsky
    Abstract:

    By genetically ablating I Kappa B kinase (IKK)-mediated activation of the transcription factor NF-Kappa B in the B cell lineage and by analyzing a mouse mutant in which Immunoglobulin lambda-Chain-positive B cells are generated in the absence of rearrangements in the locus encoding Immunoglobulin Kappa-Chain, we define here two distinct, consecutive phases of early B cell development that differ in their dependence on IKK-mediated NF-Kappa B signaling. During the first phase, in which NF-Kappa B signaling is dispensable, predominantly Kappa-Chain-positive B cells are generated, which undergo efficient receptor editing. In the second phase, predominantly lambda-Chain-positive B cells are generated whose development is ontogenetically timed to occur after rearrangements of the locus encoding Kappa-Chain. This second phase of development is dependent on NF-Kappa B signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2.

  • rearrangement enhancing element upstream of the mouse Immunoglobulin Kappa Chain j cluster
    Science, 1996
    Co-Authors: L Ferradini, Klaus Rajewsky, H Gu, A De Smet, C A Reynaud, Jeanclaude Weill
    Abstract:

    Transcriptional regulatory elements have been shown to be necessary but not sufficient for the developmental regulation of Immunoglobulin gene rearrangement in mouse precursor B cells. In the chicken λ light Chain locus, additional elements in the V-J intervening sequence are involved in negative and positive regulation of rearrangement. Here, mutation of the mouse homolog of a chicken element, located in the Vκ-Jκ intervening sequence upstream of the Jκ cluster, was shown to significantly decrease rearrangement. This cis-acting recombination-enhancing element affects the rearrangement process without being involved in regulating transcription.

T Sitnikova - One of the best experts on this subject based on the ideXlab platform.

  • evolution of Immunoglobulin Kappa Chain variable region genes in vertebrates
    Molecular Biology and Evolution, 1998
    Co-Authors: T Sitnikova
    Abstract:

    : The major source of Immunoglobulin diversity is variation in DNA sequence among multiple copies of variable region (V) genes of the heavy- and light-Chain multigene families. In order to clarify the evolutionary pattern of the multigene family of Immunoglobulin light Kappa Chain V region (V Kappa) genes, phylogenetic analyses of V Kappa genes from humans and other vertebrate species were conducted. The results obtained indicate that the V Kappa genes so far sequenced can be grouped into three major monophyletic clusters, the cartilaginous fish, bony fish and amphibian, and mammalian clusters, and that the cartilaginous fish cluster first separated from the rest of the V Kappa genes and then the remaining two clusters diverged. The mammalian V Kappa genes can further be divided into 10 V Kappa groups, 7 of which are present in the human genome. Human and mouse V Kappa genes from different V Kappa groups are intermingled rather than clustered on the chromosome, and there are a large number of pseudogenes scattered on the chromosome. This indicates that the chromosomal locations of V Kappa genes have been shuffled many times by gene duplication, deletion, and transposition in the evolutionary process and that many genes have become nonfunctional during this process. This mode of evolution is consistent with the model of birth-and-death evolution rather than with the model of concerted evolution. An analysis of duplicate V Kappa functional genes and pseudogenes in the human genome has indicated that pseudogenes evolve faster than functional genes but that the rate of nonsynonymous nucleotide substitution in the complementarity-determining regions of V Kappa genes has been enhanced by positive Darwinian selection.

Steffen Jung - One of the best experts on this subject based on the ideXlab platform.

Soldano Ferrone - One of the best experts on this subject based on the ideXlab platform.

Raul Mostoslavsky - One of the best experts on this subject based on the ideXlab platform.

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