scholarly journals Lack of feedback inhibition of V kappa gene rearrangement by productively rearranged alleles.

1991 ◽  
Vol 173 (2) ◽  
pp. 409-415 ◽  
Author(s):  
K Harada ◽  
H Yamagishi
Keyword(s):  
Gene Rearrangement ◽  
Feedback Inhibition ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Immunoglobulin Kappa ◽  
Kappa Chain ◽  
Double Recombination ◽  
Circular Dnas ◽  
Reading Frames ◽  
Multiple Recombination

Circular DNAs excised by immunoglobulin kappa chain gene rearrangements were cloned and characterized. 16 of 17 clones examined were double recombination products containing a V kappa-J kappa rearrangement (coding joint) as well as the reciprocal element (signal joint) of another V kappa-J kappa rearrangement. These products suggested multiple recombination, primary inversion, and secondary excision. In primary events, 5 of 16 translational reading frames were in-phase. Thus, V kappa gene rearrangement may not be inhibited by the presence of a productively rearranged allele. An unusually large trinucleotide (P) insertion forming a palindrome of 12 nucleotides was also observed in one of the coding joints.

Structure of extrachromosomal circular DNAs generated by immunoglobulin light chain gene rearrangements

1991 ◽  
Vol 27 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Toshiyasu Hirama ◽  
Sunao Takeshita ◽  
Yataroh Yoshida ◽  
Hideo Yamagishi
Keyword(s):  
Light Chain ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Circular Dnas

scholarly journals The active immunoglobulin kappa chain gene is packaged by non-ubiquitin-conjugated nucleosomes.

1986 ◽  
Vol 83 (11) ◽  
pp. 3738-3742 ◽  
Author(s):  
S. Y. Huang ◽  
M. B. Barnard ◽  
M. Xu ◽  
S. Matsui ◽  
S. M. Rose ◽  
...  
Keyword(s):  
Chain Gene ◽  
Immunoglobulin Kappa ◽  
Kappa Chain

Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1518-1528
Author(s):  
WD Ludwig ◽  
CR Bartram ◽  
J Ritter ◽  
A Raghavachar ◽  
W Hiddemann ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Molecular Genetic ◽  
Surface Marker ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Ig Heavy Chain

Ambiguous phenotypes and genotypes were observed in 16 children with acute leukemia. Surface marker, cytogenetic, molecular genetic, and DNA flow cytometric analyses as well as standard morphologic and cytochemical studies were used to divide the patients into three groups. The first group comprised five children with acute leukemia whose blast cells were morphologically lymphoid, while immunophenotyping disclosed simultaneous expression of early pre-B cell and myeloid features. Molecular genetic studies showed evidence of heavy-chain immunoglobulin (Ig) gene rearrangements in all patients. Cytogenetic data, available in three of these children, revealed t(4;11). In five of the 16 patients, morphologic and surface marker analyses indicated the coexistence of two separate cell populations, one with myeloid and the other with early pre-B cell features. Further evidence of B cell commitment in these patients was provided by demonstration of Ig heavy-chain gene rearrangements in all five patients. Surprisingly, one of the five patients showed oligoclonal Ig heavy-chain as well as monoclonal gene rearrangement for the beta chain of the T cell receptor (beta-TCR). The last group consisted of four cases with otherwise typical acute lymphoblastic leukemia (ALL), early pre-B cell phenotype, and coexpression of myeloid or T cell-associated antigens, and two children with unequivocal acute myeloid leukemia (AML) and coexpression of T cell antigens. Gene rearrangement of Ig heavy-chain could be demonstrated in five of six patients, additional Ig light-chain gene rearrangement in two children with ALL, and bigenotypic features (Ig heavy-chain and beta-TCR gene rearrangement) in one patient. In none of the 16 patients did flow cytometry disclose clonal abnormalities of leukemic cell DNA content. Based on these findings, we suggest that malignant transformation in the first and second group of patients took place at a stage ontogenetically close to the pluripotent stem cell, whereas ambiguous phenotypes in the third group resulted from aberrant gene expression or insufficient reagent specificity.

scholarly journals Silencing of the expression of the immunoglobulin kappa gene in non-B cells

1991 ◽  
Vol 11 (3) ◽  
pp. 1431-1437
Author(s):  
J W Pierce ◽  
A M Gifford ◽  
D Baltimore
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Types ◽  
Chain Gene ◽  
Nf Kappa B ◽  
Activated T Cells ◽  
Independent Manner ◽  
Immunoglobulin Kappa ◽  
Kappa Chain ◽  
B Lineage

Although the activating factor NF-kappa B can be present in the nucleus of many cell types, transcription and rearrangement of the immunoglobulin kappa chain gene is restricted to cells of the B lineage. Part of this specificity is determined by sequences within the major intron of the kappa gene that specifically silence gene expression in non-B cells (T cells and HeLa cells). These sequences are found in a 232-bp fragment located 5' of the NF-kappa B binding sequence of the enhancer. When this fragment is added back upstream of an active NF-kappa B site, it specifically decreases the expression of a linked gene by more than 10-fold in activated T cells but it has no effect on expression in B cells. The kappa silencer region acts in an orientation- and distance-independent manner and appears to be composed of multiple negative elements. The kappa silencer may act to restrict transcription and rearrangement of the C kappa locus to cells of the B lineage.

Somatic Mutations Within the Untranslated Regions of Rearranged Ig Genes in a Case of Classical Hodgkin’s Disease as a Potential Cause for the Absence of Ig in the Lymphoma Cells

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3964-3972 ◽  
Author(s):  
Andrea Jox ◽  
Thomas Zander ◽  
Ralf Küppers ◽  
Johannes Irsch ◽  
Holger Kanzler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hodgkin's Disease ◽  
Gene Rearrangement ◽  
Somatic Mutations ◽  
Hodgkin’S Disease ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Northern Blot Hybridization ◽  
Light Chain Gene ◽  
Octamer Motif

Abstract Hodgkin–Reed-Sternberg (H-RS) cells are clonal B cells carrying Ig gene rearrangements. However, in situ hybridization methods failed to demonstrate Ig gene expression in H-RS cells of classical Hodgkin’s disease (HD). Because somatic mutations rendering potentially functional Ig gene rearrangements nonfunctional were detected in some cases of the disease, it was speculated that H-RS cells in classical HD may have lost the ability to express antigen receptor as a rule. Recently, we established a novel cell line (L1236) from H-RS cells of a patient with mixed cellularity subtype of HD. L1236 cells harbor a potentially functional VH1 and a potentially functional Vκ3 gene rearrangement. However, no antibody expression was detected. To show potential reasons for this lack of Ig expression, we analyzed the genomic organization of the Ig genes and their transcription in the primary and cultivated H-RS cells of this patient. The H-RS cells were found to have switched their isotype to IgG4, confirming their mature B-cell nature. By amplifying cDNA from L1236 cells as well as from frozen biopsy material transcripts of the Vκ3 and the VH1 gene rearrangement were detected for both sources of cDNA. However, Northern blot hybridization of L1236 RNA failed to demonstrate VH1 and Vκ3 transcripts, indicating only a low level of transcription. Sequence analysis of the promoter and leader regions of the VH1 gene rearrangement from L1236 cells as well as from lymphoma-affected tissue showed a somatic mutation in the conserved octamer motif of the promoter region. Somatic mutations were also detected within the 3′ splice site of the leader intron and adjacent nucleotides in the rearranged Vκ light chain gene, leading to aberrant splicing. These mutations might prevent the generation of adequate amounts of functional Ig gene transcripts as template for translation into protein. Thus, mutations in H-RS cells that prevent Ig gene expression might also be located outside the coding region of the Ig genes.

scholarly journals Rearrangements of T-cell antigen receptor delta chain gene in hematologic neoplasms

Blood ◽  
1989 ◽  
Vol 74 (8) ◽  
pp. 2707-2712 ◽  
Author(s):  
N Asou ◽  
T Hattori ◽  
M Matsuoka ◽  
F Kawano ◽  
K Takatsuki
Keyword(s):  
T Cell ◽  
B Cell ◽  
Gene Rearrangement ◽  
Antigen Receptor ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Delta Gene

Abstract Rearrangements of the T-cell antigen receptor (TCR) delta chain gene were studied in primary neoplastic cells from 137 patients with leukemia or lymphoma. TCR delta gene rearrangements or deletions were observed in all 50 T-cell neoplasms: 5 of 8 CD3- T-cell neoplasms showed rearrangements, whereas biallelic deletion of TCR delta gene was the most common pattern in CD3+ T-cell neoplasm (39 of 42 patients). Rearrangements of TCR delta gene were also detected in 23 of 40 immature B-cell leukemias, including 22 of 25 patients with rearrangements of TCR gamma gene, 2 of 17 mature B-cell neoplasms, and 3 of 30 myeloid leukemias. Thus, TCR delta gene rearrangement or deletion is always found in T-cell neoplasms and is frequently found in immature B-cell leukemias associated with TCR gamma gene rearrangement. Furthermore, TCR delta gene rearrangements associated with the germline configuration of the TCR beta, gamma, and immunoglobulin heavy chain genes were observed in two immature T-cell leukemias, suggesting that TCR delta gene rearrangements precede TCR gamma and beta gene rearrangements. These results indicate that an analysis of TCR delta gene rearrangement provides potential tools to establish the clonality of immature T-cell neoplasms and to identify the normal stages of lymphocyte differentiation.

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