The human VK locus

Straubinger, Bernhard; Huber, Erwin; Lorenz, Wulfing; Osterholzer, Eva; Pargent, Walter; Pech, Michael; Pohlenz, Hans-Dieter; Zimmer, Franz-Josef; Zachau, Hans G.

doi:10.1016/0022-2836(88)90376-2

Cited by 91 publications

(37 citation statements)

References 32 publications

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“…Some of them have already been published [4,[19][20][21] and some pseudogenes will be compiled together with pseudogenes from other regions of the x locus (K. F. Schable et al, in preparation). In the present report the sequences of eight potentially functional V, genes (or genes with only minor defects) of the A regions are described and reference to the systematic survey of the A region genes in [4] is given. Since all nucleic acid sequences are being transmitted to the EMBL Data Library and for most genes the sequencing strategies are available in dissertations, we restrict ourselves here in most cases to reporting the formal translation products of the genes.…”

Section: The V Genes Of the A Regionsmentioning

confidence: 99%

“…The gene A19 was sequenced in the p313 subclones by a strategy analogous to that published for its duplicate A3 [4]. Since the coding parts of the two genes are identical, no sequences are shown.…”

Section: The V Genes Of the A Regionsmentioning

confidence: 99%

“…In addition to the cosmid clones described in [4] the following ones are shown: cos 256 [14]; cos 146, cos 149, and cos 607/7 [3]; cos 60711-3 were isolated and mapped by H. G. Klobeck and G.…”

Section: Recombinant Dna Librariesmentioning

confidence: 99%

“…The reagents and techniques were essentially the same as in [3,4]. All sequences have been submitted to the EMBL Data Library.…”

Section: Enzymes Reagents Blot Hybridization Sequencingmentioning

confidence: 99%

“…Large parts of the locus turned out to be duplicated, giving rise to a C,-proximal (p) copy and a similar, but not identical, distal (d) copy. In the course of the work three fully or partly duplicated "regions" and one unique region emerged from the respective contigs: Op/Od [3], Ap/Ad [4], Lp/Ld [5], and the B-J,-C, region [6,7]. Several structural and functional aspects of the x locus have been reviewed [S, 91 and a general overview was given in a recent study on polymorphisms and haplotypes in the locus [lo].…”

Section: Introductionmentioning

confidence: 99%

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The human immunoglobulin x locus. Characterization of the duplicated A regions

et al. 1992

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The central regions of the kappa locus, the so-called A regions, have been fully characterized on cosmid and phage lambda clones. The regions, which are parts of the C kappa-proximal and -distal copies of the locus and are, therefore, called Ap and Ad regions, comprise about 140 kb each and contain together 30 V kappa genes and pseudogenes. The A regions have been linked on their 5' sides to the O regions and on their 3' sides to the L regions. Chromosomal walking has eliminated a previous gap in the Ap region. Detailed restriction maps of the Ap and Ad regions and the sequences of 9 V kappa genes are reported. Four events, which have occurred in evolution probably after the duplication of the A region, were identified: the insertion of an Alu element in Ad; the insertion of part of a LINE element in Ap; the deletion of a 17.5-kb fragment including one V kappa gene from Ap; the sequence divergence of duplicated V kappa gene regions which ranges among the five pairs studied here from 0 to 14 bp per kb and converted two genes to pseudogenes while their duplicates stayed functional. An analysis of the A regions of the lymphoid cell lines RPMI 6140 and GM607 confirmed the previous finding that the V kappa-J kappa rearrangement in these cell lines had occurred by deletion and inversion mechanisms, respectively. Thus, the structural data contribute to the understanding of the evolution and the functioning of the A regions of the kappa locus.

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Section: The V Genes Of the A Regionsmentioning

confidence: 99%

Section: The V Genes Of the A Regionsmentioning

confidence: 99%

Section: Recombinant Dna Librariesmentioning

confidence: 99%

“…The reagents and techniques were essentially the same as in [3,4]. All sequences have been submitted to the EMBL Data Library.…”

Section: Enzymes Reagents Blot Hybridization Sequencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The human immunoglobulin x locus. Characterization of the duplicated A regions

et al. 1992

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Re-expression of RAG-1 and RAG-2 genes and evidence for secondary rearrangements in human germinal center B lymphocytes

1998

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V(D)J recombination occurs in immature B cells within primary lymphoid organs. However, recent evidence demonstrated that the recombination activating genes RAG-1 and RAG-2 can also be expressed in murine germinal centers (GC) where they can mediate secondary rearrangements. This finding raises a number of interesting questions, the most important of which is what is the physiological role, if any, of secondary immunoglobulin (Ig) gene rearrangements. In the present report, we provide evidence that human GC B cells that have lost surface immunoglobulin re-express RAG-1 and RAG-2, suggesting that they may be able to undergo Ig rearrangement. Furthermore, we describe two mature B cell clones in which secondary rearrangements have possibly occurred, resulting in light chain replacement. The two clones carry both kappa and lambda light chains productively rearranged, but fail to express the x chain on the cell surface due to a stop codon acquired by somatic mutation. Interestingly, the analysis of the extent of somatic mutations accumulated by the two light chains might suggest that the lambda chain could have been acquired through a secondary rearrangement. Taken together, these data suggest that secondary Ig gene rearrangements leading to replacement may occur in human GC and may contribute to the peripheral B cell repertoire.

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Molecular mimicry between bacterial and self antigen in a patient with systemic lupus erythematosus

1999

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The importance of microbial infection as a trigger for the induction of systemic lupus erythematosus is frequently debated. Clinical observations indicate that anti-viral and antibacterial responses are often accompanied by self reactivity, and anti-pneumococcal antibodies elicited in non-autoimmune individuals by pneumococcal vaccine express lupusassociated anti-DNA idiotypes. To explore the relationship between protective and pathogenic antibodies in humans, we have used the phage display immunoglobulin expression system to generate a combinatorial library from spleen cells of a lupus patient immunized with a polyvalent pneumococcal polysaccharide vaccine prior to splenectomy. From this library, monovalent antigen-binding fragments expressing the 3I V O 1-associated idiotype were isolated. This idiotype is expressed on up to 90 % of anti-DNA antibodies in the serum of lupus patients and on anti-pneumococcal antibodies in the serum of non-autoimmune individuals. Eight 3I + monovalent antigen-binding fragments reacting with pneumococcal polysaccharide, DNA or both were analyzed. Four of these fragments were cross-reactive with both foreign and self antigen, demonstrating that a high percentage of anti-bacterial antibodies produced in a patient with lupus bind double-stranded DNA. These studies provide support at the molecular level for a potential role of molecular mimicry in the generation of anti-DNA antibodies. In addition, this is, to our knowledge, the first panel of fully sequenced human anti-pneumococcal antibodies.

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The human VK locus

Cited by 91 publications

References 32 publications

The human immunoglobulin x locus. Characterization of the duplicated A regions

The human immunoglobulin x locus. Characterization of the duplicated A regions

Re-expression of RAG-1 and RAG-2 genes and evidence for secondary rearrangements in human germinal center B lymphocytes

Molecular mimicry between bacterial and self antigen in a patient with systemic lupus erythematosus

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