Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer

1989 ◽  
Vol 9 (10) ◽  
pp. 4239-4247
Author(s):  
R A Currie ◽  
R G Roeder
Keyword(s):  
B Cell ◽  
Binding Site ◽  
Light Chain ◽  
Specific Binding ◽  
Specific Factor ◽  
Immunoglobulin Gene ◽  
Kappa Light Chain ◽  
Nf Kappa B ◽  
Light Chain Immunoglobulin ◽  
A Site

A 215-base-pair (bp) region of the mouse MOPC 41 kappa light-chain immunoglobulin gene enhancer has been analyzed for specific binding of lymphoid and nonlymphoid nuclear factors. Mobility shift assays with a series of overlapping DNA fragments have mapped DNA-binding sites for three unique factors. The B-cell-specific (OTF-2) and ubiquitous (OTF-1) octamer-binding transcription factors specifically bound to a site centered about 136 bp 5' of the nuclear factor NF-kappa B site. A third specific factor, NF-kappa E, bound to a site that was about 75 bp 5' of the NF-kappa B site and within a region important for enhancer function. This novel factor was found in both mature B and HeLa cell nuclei. B-cell OTF-2, B-cell OTF-1, and HeLa OTF-1 bound to the kappa enhancer and kappa promoter octamer sites with similar affinities despite a 2-bp difference in the kappa enhancer octamer sequence. However, DNase I footprint analyses indicated that affinity-purified OTF-2 bound both to the enhancer OTF site and, surprisingly, to 80 bp of A + T-rich flanking sequence. Moreover, methylation interference studies demonstrated distinct differences in OTF interactions between the consensus octamer in the kappa promoter and the nonconsensus octamer identified in the enhancer. This novel observation of an OTF-binding site in the kappa enhancer provides a common link with the OTF sites in the promoter-proximal regions of all kappa promoters and thus mirrors the structural arrangement of OTF sites found in the promoters and enhancers of immunoglobulin heavy-chain genes.

scholarly journals Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer.

1989 ◽  
Vol 9 (10) ◽  
pp. 4239-4247 ◽  
Author(s):  
R A Currie ◽  
R G Roeder
Keyword(s):  
B Cell ◽  
Binding Site ◽  
Light Chain ◽  
Specific Binding ◽  
Specific Factor ◽  
Immunoglobulin Gene ◽  
Kappa Light Chain ◽  
Nf Kappa B ◽  
Light Chain Immunoglobulin ◽  
A Site

A 215-base-pair (bp) region of the mouse MOPC 41 kappa light-chain immunoglobulin gene enhancer has been analyzed for specific binding of lymphoid and nonlymphoid nuclear factors. Mobility shift assays with a series of overlapping DNA fragments have mapped DNA-binding sites for three unique factors. The B-cell-specific (OTF-2) and ubiquitous (OTF-1) octamer-binding transcription factors specifically bound to a site centered about 136 bp 5' of the nuclear factor NF-kappa B site. A third specific factor, NF-kappa E, bound to a site that was about 75 bp 5' of the NF-kappa B site and within a region important for enhancer function. This novel factor was found in both mature B and HeLa cell nuclei. B-cell OTF-2, B-cell OTF-1, and HeLa OTF-1 bound to the kappa enhancer and kappa promoter octamer sites with similar affinities despite a 2-bp difference in the kappa enhancer octamer sequence. However, DNase I footprint analyses indicated that affinity-purified OTF-2 bound both to the enhancer OTF site and, surprisingly, to 80 bp of A + T-rich flanking sequence. Moreover, methylation interference studies demonstrated distinct differences in OTF interactions between the consensus octamer in the kappa promoter and the nonconsensus octamer identified in the enhancer. This novel observation of an OTF-binding site in the kappa enhancer provides a common link with the OTF sites in the promoter-proximal regions of all kappa promoters and thus mirrors the structural arrangement of OTF sites found in the promoters and enhancers of immunoglobulin heavy-chain genes.

scholarly journals NF-kappa B binds within a region required for B-cell-specific expression of major histocompatibility complex class II gene E alpha d.

1989 ◽  
Vol 9 (2) ◽  
pp. 844-846 ◽  
Author(s):  
M A Blanar ◽  
L C Burkly ◽  
R A Flavell
Keyword(s):  
Major Histocompatibility Complex ◽  
B Cell ◽  
Major Histocompatibility Complex Gene ◽  
Specific Factor ◽  
Major Histocompatibility ◽  
Nf Kappa B ◽  
Specific Expression ◽  
Histocompatibility Complex ◽  
A Site ◽  
Cell Expression

A region upstream of the murine major histocompatibility complex gene, E alpha d, has been shown previously to be required for B-cell expression. Binding of the B-cell-specific factor, NF-kappa B, to a site within this region is indistinguishable from that observed with the kappa enhancer binding site. NF-kappa B may be responsible for E alpha d B-cell expression.

NF-kappa B binds within a region required for B-cell-specific expression of major histocompatibility complex class II gene E alpha d

1989 ◽  
Vol 9 (2) ◽  
pp. 844-846
Author(s):  
M A Blanar ◽  
L C Burkly ◽  
R A Flavell
Keyword(s):  
Major Histocompatibility Complex ◽  
B Cell ◽  
Major Histocompatibility Complex Gene ◽  
Specific Factor ◽  
Major Histocompatibility ◽  
Nf Kappa B ◽  
Specific Expression ◽  
Histocompatibility Complex ◽  
A Site ◽  
Cell Expression

A region upstream of the murine major histocompatibility complex gene, E alpha d, has been shown previously to be required for B-cell expression. Binding of the B-cell-specific factor, NF-kappa B, to a site within this region is indistinguishable from that observed with the kappa enhancer binding site. NF-kappa B may be responsible for E alpha d B-cell expression.

scholarly journals Regulation and a possible stage-specific function of Oct-2 during pre-B-cell differentiation.

1991 ◽  
Vol 11 (10) ◽  
pp. 4885-4894 ◽  
Author(s):  
C L Miller ◽  
A L Feldhaus ◽  
J W Rooney ◽  
L D Rhodes ◽  
C H Sibley ◽  
...  
Keyword(s):  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Interleukin 1 ◽  
Transcriptional Level ◽  
Immunoglobulin Gene ◽  
B Cell Differentiation ◽  
Nf Kappa B ◽  
Specific Expression

The Oct-2 gene appears to encode a developmental regulator of immunoglobulin gene transcription. We demonstrate that the Oct-2 gene is expressed at low levels in a variety of transformed pre-B-cell lines and is induced specifically in these cells by lipopolysaccharide signalling. This work extends an earlier observation in the pre-B-cell line 70Z/3 and therefore suggests that the inducible expression of the Oct-2 gene, like that of the kappa gene, is a characteristic feature of the pre-B stage of B-cell development. In 70Z/3 cells, the lymphokine interleukin-1 also induces the expression of the Oct-2 and kappa loci. Interestingly, expression of the Oct-2 gene is rapidly induced at the transcriptional level and may not require de novo protein synthesis. Since the changes in the activity of the Oct-2 locus completely correlate with the changes of the activity of the kappa locus, the two genes may be transcriptionally regulated by a common trans-acting factor. In 70Z/3 cells, transforming growth factor beta, an inhibitor of kappa-gene induction, blocks the upregulation of Oct-2 but not the activation of NF-kappa B. These results suggest that the combinatorial action of increased levels of Oct-2 and activated NF-kappa B may be necessary for the proper stage-specific expression of the kappa locus.

scholarly journals The added value of immunoglobulin Kappa light chain gene (IGK) rearrangement analysis in suspected B-cell lymphomas: three illustrative cases

2012 ◽  
Vol 5 (1-2) ◽  
pp. 45-56 ◽  
Author(s):  
Paula Gameiro ◽  
Marta Sebastião ◽  
Signe Spetalen ◽  
Maria Gomes da Silva ◽  
José Cabeçadas
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Added Value ◽  
Chain Gene ◽  
Kappa Light Chain ◽  
B Cell Lymphomas ◽  
Light Chain Gene ◽  
Immunoglobulin Kappa

Immunoglobulin M Heavy/Light Chain Pair Measurement Independently Predicts Clinical Outcome and Refines Prognostic Information Provided By Interim PET in Patients with Aggressive Lymphomas

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3880-3880
Author(s):  
Patricia Johansson ◽  
Jan Dürig ◽  
Jan Rekowski ◽  
Stefan P Müller ◽  
Bernd Hertenstein ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Binding Site ◽  
Light Chain ◽  
Research Funding ◽  
Prognostic Value ◽  
Immunoglobulin M ◽  
Prognostic Information ◽  
Interim Pet ◽  
Aggressive Lymphomas

Abstract Introduction: We recently reported the first results of the large multicenter phase III PETAL trial (EudraCT 2006-001641-33, NCT00554164) showing that 18-fluorodeoxyglucose interim PET (iPET) performed after two cycles of chemotherapy is highly predictive of clinical outcome in patients with aggressive lymphomas. Here, the study`s biobank was utilized to exploratively investigate the prognostic value of immunoglobulin M heavy/light chain pair (HLC-M) abnormalities in this patient cohort. Methods: HLC-M κ and λ were measured in pre-treatment serum samples of a representative subset (N=187, 22%) of patients employing the Hevylite® assay (The Binding Site Ltd, Birmingham, UK). Normal HLC-M ratios and concentrations were defined according to the manufacturer`s recommendations. For statistical analysis standard time-to-event methodology (Kaplan-Meier method, Log Rank test, Cox regression) was used. Results: Median age of the 187 pts was 57 years (range 18-80), whereof 92 (49%) were male, and 95 (51%) were female. 174 pts. had CD20-positive B cell lymphomas (73% diffuse large B cell, 13% other aggressive B cell lymphomas, 7% follicular lymphoma grade 3), 13 had peripheral T cell lymphomas (7%). Normal HLC-M were observed in 150 patients (75.8%). 37/187 (20%) of the patients exhibited a monoclonal IgMκ/IgMλ ratio, where 17 (46%) showed a ratio below and 20 (54%) above the reference range. HLC-M abnormalities were significantly associated with adverse clinical characteristics including advanced Ann Arbor stage (p=0.005), high international prognostic index (IPI, p=0.001) and extranodal disease (p=0.003). Patients with abnormal HLC-M ratios had inferior time to treatment failure (TTTF, Figure 1) and overall survival (OS, Figure 2) as compared to their counterparts with normal HLC-M ratios. Of note, subgroup analyses revealed that the prognostic value of HLC-M abnormalities was limited to patients with a favorable iPET and low-intermediate IPI score. In multivariate analysis with the cox model and controlling for the IPI factors (including age), histology, sex as well as FLC κ and λ, monoclonal HLC-M remained predictive for a shorter TTTF (p=0.0181, covariate-adjusted hazard ratio (aHR) 2.195, 95% CI [1.144;4.214]) and OS (p=0.0034, aHR 3.844, 95% CI [1.559;9.476]). Conclusions: Monoclonal HLC-M is an independent predictor of survival in patients with aggressive lymphoma and refines prognostic information provided by iPET and IPI. Figure 1. Figure 1. Disclosures Dürig: The Binding Site: Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Roche: Consultancy, Other: Travel support, Speakers Bureau; Aicuris: Consultancy; Celgene: Consultancy, Other: Travel support, Speakers Bureau. La Rosée:Roche: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; CTI Lifesciences: Honoraria; Janssen-Cilag: Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Research Funding; Mundipharma: Other: Travel support; Takaeda: Consultancy, Honoraria, Other: travel support; Celgene: Honoraria. Dührsen:Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria, Research Funding. Hüttmann:Amgen: Consultancy, Research Funding; Gilead: Consultancy; Takeda: Consultancy, Other: Travel support; Roche: Research Funding; Celgene: Other: Travel support, Speakers Bureau.

scholarly journals Identification of an octamer-binding site in the human kappa light-chain enhancer.

1990 ◽  
Vol 10 (7) ◽  
pp. 3843-3846 ◽  
Author(s):  
K Nelms ◽  
B Van Ness
Keyword(s):  
Binding Site ◽  
Heavy Chain ◽  
Light Chain ◽  
Tissue Specificity ◽  
Chain Gene ◽  
Gene Promoters ◽  
Kappa Light Chain ◽  
Light Chain Gene ◽  
Gene Enhancer ◽  
Light Chain Enhancer

Octamer motifs contribute to the function and tissue specificity of immunoglobulin heavy- and light-chain gene promoters and the heavy-chain enhancer. A variant octamer-binding site within a conserved region of the human kappa light-chain gene enhancer which contributes to the function of this enhancer has been identified.

scholarly journals Autoantibody-associated cross-reactive idiotypes expressed at high frequency in chronic lymphocytic leukemia relative to B-cell lymphomas of follicular center cell origin

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 422-428 ◽  
Author(s):  
TJ Kipps ◽  
BA Robbins ◽  
P Kuster ◽  
DA Carson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Light Chain ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
Kappa Light Chain ◽  
Region Gene ◽  
Variable Regions ◽  
Hodgkin's Lymphomas ◽  
Center Cell

Using murine monoclonal antibodies (MoAbs) specific for immunoglobulin (Ig) cross-reactive idiotypes (CRI), we performed immunohistochemical analyses on frozen tissue sections and cytocentrifuge preparations of Ig-expressing malignant cells from patients with chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphomas (NHL) of follicular center cell origin. Twenty percent (4/20) of the Ig kappa light chain- expressing CLL cells reacted with 17.109, a MoAb against a major CRI on human IgM autoantibodies that is encoded by a conserved Ig variable- region gene (V gene) of the V kappa IIIb sub-subgroup. Another MoAb specific for V kappa IIIb framework determinant(s) reacted exclusively with all the 17.109-reactive CLL cells. Only one of 20 kappa light- chain-expressing CLL cells reacted with 6B6.6, a monoclonal antibody specific for a CRI commonly found on rheumatoid factor (RF) paraproteins with light-chain variable regions of the V kappa IIIa sub- subgroup. Finally, greater than 20% (8/34) of all CLL reacted with G6, a MoAb specific for an Ig heavy chain-associated CRI present on several RF paraproteins. In contrast, these CRIs were expressed at significantly lower frequencies in NHL of follicular center cell origin. Only one of 30 NHL expressing kappa light chains reacted with the 17.109 MoAb. Also, in contrast to the concordance between the 17.109-CRI and V kappa IIIb framework determinant(s) in CLL, two lymphomas in addition to the 17.109-reactive lymphoma were recognized by the anti-V kappa IIIb framework MoAb. None of the NHL reacted with either the 6B6.6 or the G6 MoAbs. These results are the first to demonstrate that CLL and NHL differ with respect to the expression of autoantibody-associated CRIs. The data support the notion that NHL of follicular center cell origin differs from CLL in its utilization and/or somatic mutation of Ig variable-region genes. The physiological and immunotherapeutic implications of these findings are discussed.

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