The variable genes and gene families of the mouse immunoglobulin κ locus

Thiebe, Rainer; Schäble, Karlheinz F.; Bensch, Alexander; Brensing-Küppers, Jutta; Heim, Verena; Kirschbaum, Thomas; Mitlöhner, Heike; Ohnrich, Marion; Pourrajabi, Soheil; Röschenthaler, Franz; Schwendinger, Jürgen; Wichelhaus, Daniel; Zocher, Ines; Zachau, Hans G.

doi:10.1002/(sici)1521-4141(199907)29:07<2072::aid-immu2072>3.0.co;2-e

Cited by 92 publications

(97 citation statements)

References 25 publications

(38 reference statements)

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“…Interestingly, there is no strict correlation between distance from the rearranged V 38C gene and frequency of utilization of the V 4 genes in the secondary rearrangements: V genes situated over 500 kb away from the V 38C gene are utilized at the same frequency as more proximal genes. Similarly, the results of Zachau and coworkers (42) show that the frequency of expression of a V gene in splenic B cells does not depend on its distance from the J C locus. Nevertheless, in the 38C-13 variants there is a strong bias (9 of 26) toward utilization of the kf4 V gene (22,23,26), which is situated only 30 kb from the V 38C gene.…”

Section: Discussionmentioning

confidence: 57%

Secondary V(D)J Rearrangements and B Cell Receptor-Mediated Down-Regulation of Recombination Activating Gene-2 Expression in a Murine B Cell Line

Maës

Caspi

Rougeon

et al. 2000

The Journal of Immunology

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It has recently become clear that recombination of Ig genes is not restricted to B cell precursors but that secondary rearrangements can also occur under certain conditions in phenotypically immature bone marrow and peripheral B cells. However, the nature of these cells and the regulation of secondary V(D)J recombination in response to B cell receptor (BCR) stimulation remain controversial. In the present study, we have analyzed secondary light chain gene rearrangements and recombination activating gene (RAG) expression in the surface IgM+, IgD− murine B cell line, 38C-13, which has previously been found to undergo κ light chain replacement. We find that 38C-13 cells undergo spontaneous secondary Vκ-Jκ and RS rearrangements in culture, with recombination occurring on both productive and nonproductive alleles. Both 38C-13 cells and the Id-negative variants express the RAG genes, indicating that the presence of RAG does not depend on activation via the 38C-13 BCR. Moreover, BCR cross-linking in 38C-13 cells leads to a rapid and reversible down-regulation of RAG2 mRNA. Therefore, 38C-13 cells resemble peripheral IgM+, IgD− B cells undergoing light chain gene rearrangement and provide a possible in vitro model for studying peripheral V(D)J recombination.

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Section: Discussionmentioning

confidence: 57%

Secondary V(D)J Rearrangements and B Cell Receptor-Mediated Down-Regulation of Recombination Activating Gene-2 Expression in a Murine B Cell Line

Maës

Caspi

Rougeon

et al. 2000

The Journal of Immunology

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“…In the human IGH locus, this goal is nearly complete (1), but for experimental manipulation these loci must be characterized in the mouse. Recently, the mouse L chain locus was extensively described by Zachau and colleagues (2). All Igk constant, joining, and variable coding elements have been identified and sequenced.…”

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confidence: 99%

A Three-Megabase Yeast Artificial Chromosome Contig Spanning the C57BL Mouse Igh Locus

Chevillard

Ozaki

Herring

et al. 2002

The Journal of Immunology

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The mouse Ig H chain (Igh) complex locus is composed of >100 gene segments encoding the variable, diversity, joining, and constant portions of the Ab H chain protein. To advance the characterization of this locus and to identify all the VH genes, we have isolated the entire region from C57BL/6 and C57BL/10 as a yeast artificial chromosome contig. The mouse Igh locus extends approximately three megabases and contains at least 134 VH genes classified in 15 partially interspersed families. Two non-Igh pseudogenes (Odc-rs8 and Rpl32-rs14) were localized in the distal part of the locus. This physical yeast artificial chromosome map will provide important structure and guidance for the sequencing of this large, complex, and highly repetitive locus.

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“…We were not able to close the last three small gaps of together about 90 kb before my retirement, but we hope this will soon be done by others. 140 V genes and pseudogenes, as well as a few V relics and orphons, were localized and sequenced Thiebe et al, 1999;Röschenthaler et al, 1999Röschenthaler et al, , 2000; a detailed restriction map of the locus and supplementary information can be found on our homepage). The mouse locus is three times larger and has nearly twice as many V genes as the human locus.…”

Section: Work On Immunoglobulin Genes In Munichmentioning

confidence: 99%

The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach

Zachau

2000

Biological Chemistry

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Some aspects of the work of our group on the human and mouse immunoglobulin genes are reviewed. The human locus contains a large duplication: a 600 kb C -proximal copy with 40 V genes is found in the close vicinity of a 440 kb C -distal copy with 36 very similar, but not identical, V genes. The chimpanzee has only the C -proximal copy of the locus. The locus of the mouse is close to 3.2 Mb in size, of which 3.1 Mb have been cloned in four contigs, leaving three small gaps of together about 90 kb; 140 V genes and pseudogenes were localized and sequenced. In parallel to the elucidation of the structure of the loci, the mechanisms of the V-J rearrangement, somatic hypermutation and gene expression were studied. Various polymorphisms were detected in the human population and a number of haplotypes defined. In addition to the V genes within the loci numerous V orphons were localized on different chromosomes. Comparing the loci of different species allows some interesting conclusions as to the evolution of this multigene family. Finally our strategy of elucidating the structure and function of the loci, which has been termed a 'cottage industry approach', is discussed in relation to the large-scale genome analysis as pursued today using automated methods. Key words: Contigs / Human / Immunoglobulin locus / Mouse.The genes and loci of the immunoglobulin heavy and light chains have been reviewed by Honjo and Alt (1995) and by Max (1999). A wealth of structural and functional data is also available on the Internet (Immunoglobulin gene databases, 1999). Work on Immunoglobulin Genes in MunichIn our laboratory the work on immunoglobulin genes started in the late '70s with experiments in which the chromatin structure of expressed genes in mouse myelomas was compared to the chromatin structure of the corresponding silent genes in mouse liver. In the following years both chromatin and immunoglobulin gene projects were pursued in our laboratory, but it turned out that the chromatin work was slow-moving and not very informative. On the other hand, at that time Tonegawa discovered the recombination of variable, joining and constant (V, J, C) gene segments and many researchers, including us, were intrigued by the new possibilities of cloning and analyzing mammalian genes. We found the reciprocal recombination products, now called signal joints (Steinmetz et al., 1980), contributed to the understanding of somatic mutations (Pech et al., 1981) and defined the immunoglobulin gene promoter (Falkner and Zachau, 1984). The last chromatin project in our lab came to an end in 1984. A few years later chromatin research picked up momentum worldwide again, but by then we were fully engaged in work on immunoglobulin genes and did not return to chromatin.After working on immunoglobulin genes for a few years we felt that in order to understand certain functional and mechanistic aspects, we should know all V, J and C genes in at least one of the loci. Therefore in 1982 we embarked on an attempt to clone all human immunoglobulin V genes. 12 year...

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The variable genes and gene families of the mouse immunoglobulin κ locus

Cited by 92 publications

References 25 publications

Secondary V(D)J Rearrangements and B Cell Receptor-Mediated Down-Regulation of Recombination Activating Gene-2 Expression in a Murine B Cell Line

Secondary V(D)J Rearrangements and B Cell Receptor-Mediated Down-Regulation of Recombination Activating Gene-2 Expression in a Murine B Cell Line

A Three-Megabase Yeast Artificial Chromosome Contig Spanning the C57BL Mouse Igh Locus

The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach

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