Establishment in continuous culture of a new type of lymphocyte from a “burkitt‐like” malignant lymphoma (line d.g.‐75)

Ben‐Bassat, Hannah; Goldblum, Natan; Mitrani, Stella; T, Goldblum; Yoffey, J. M.; Cohen, Maimon M.; Bentwich, Zvi; Ramot, Bracha; Klein, Eva; Klein, George

doi:10.1002/ijc.2910190105

Cited by 261 publications

(144 citation statements)

References 32 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…IRF1 was originally cloned from a cDNA expression library based on its affinity for a synthetic oligonucleotide (AAGTGA) 4 . A single hexamer of this sequence and several similar purine-rich hexamers were found in the virus-inducible region of the IFN-␤ promoter, and IRF1 was believed to be responsible for both virus-induced transcription of the IFN-␤ gene and upregulation of transcription of genes induced by IFN-␣/␤ (50).…”

Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Schaefer

Paulson

Strominger

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) infection in immunocompetenthumans is predominantly latent and persists for the life of the individual (reviewed in reference 41). Recently, it has been shown that EBV is capable of adopting at least three distinct forms of latency (27). Type III latency is observed upon in vitro infection of B lymphocytes and results in immortalization and continuous proliferation of the infected B cells via the action of a subset of the six EBV nuclear antigens (EBNAs; EBNA1, EBNA2, EBNA3a, EBNA3b, EBNA3c, and EBNA4) and three membrane proteins (LMP1, LMP2a, and LMP2b) expressed in the type III (immortalizing) program. However, in vivo, the type III latency program is likely to be only transiently observed upon initial infection of a naive host, since several of the type III latent antigens elicit a potent cytotoxic T-lymphocyte response resulting in very effective elimination of type III latently infected B cells (reviewed in reference 33).EBV is also capable of entering programs of latency in which the expression of latent antigens is restricted with respect to the type III program. In type I latency, only the EBNA1 protein is expressed (64). It has recently been shown that EBNA1 peptides do not enter the major histocompatibility complex class I antigen processing and presentation pathway (29, 39, 52), and cells which express only EBNA1 are not detected by host cellular immune surveillance mechanisms (63). The type II latency program differs from type I latency only in the expression of variable combinations of LMP1, LMP2a, and LMP2b, in addition to EBNA1. Since the type I latency program was identified, there has been speculation that type I latently infected B lymphocytes represent the lifelong reservoir of virus in immunocompetent, seropositive individuals, and there have recently been several reports which provide evidence that a type I-like form of restricted viral latency does indeed exist in healthy carriers of EBV (6,51,60,85).Investigations into the molecular basis of type III and type I latency have demonstrated that distinct promoters are used to drive transcription of the EBNAs in each latent program. In type III latency, transcription of all six nuclear antigens is initiated from either Wp (during initial infection of resting B cells) or Cp (in cycling B cells), and the long primary transcripts are differentially spliced to generate the mature EBNA transcripts (75, 94; see Fig. 1A for a schematic representation of EBV latent transcription and locations of promoters). Recent investigations have shown that transcription of the EBNA1 gene in type I latency is driven by a promoter designated Qp, which is considerably downstream of the type III latency EBNA gene promoters (57,(70)(71)(72). Qp has an architecture with numerous similarities to eukaryotic housekeeping

show abstract

Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Schaefer

Paulson

Strominger

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…DG75 is an EBV negative Burkitt Lymphoma cell line (Ben-Basset et al, 1977) and Jurkat is a cell line derived from a EBV-negative T cell lymphoma (Brattsand et al, 1990). ELI-BL is an EBV-positive tumour line showing a latency I form of infection in which EBNA1 is the only viral protein expressed (Rowe et al, 1987b).…”

Section: Cell Linesmentioning

confidence: 99%

Epstein-Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF-κB activation

1997

View full text Add to dashboard Cite

The Epstein-Barr virus Latent Membrane Protein-1 (LMP1) has structural features and functions consistent with it being a constitutively active cell surface receptor. The known association of LMP1 with members of the TRAF family of proteins suggests that LMP1 transduces signals similarly to the Tumour Necrosis Factor Receptor (TNFR) family of cell surface receptors that signal by forming dimers or trimers in response to binding of extracellular ligands. However, interactions between LMP1 and the TRAFs have so far only been described for the C-terminal activation region 1 (CTAR1) of LMP1 and no direct interactions of the TRAFs with the second NF-kB activation domain (CTAR2) have been reported. We have now mapped the NF-kB activation domain of CTAR2 to a highly conserved stretch of 6 amino acids at the far C-terminus (codons 379 to 384 in B95.8 LMP1). In addition, we constructed chimeric receptor molecules which contain the ligand-binding extracellular domain and the transmembrane domain of rat CD2 fused to the C-terminus of LMP1 encoding the CTAR1 and/or the CTAR2 domain. Interestingly, the function of a chimera encoding CTAR2 alone, as well as the function of a chimera encoding both CTAR1 and CTAR2 was found to be inducible upon antibody-mediated crosslinking. These inducible chimeric proteins also allowed us to demonstrate that LMP1 mediated NF-kB activation is an immediate event following activation of LMP1.

show abstract

“…Ramos , DG75 (Ben-Bassat et al, 1977), Akata (Takada, 1984), Rael (Klein et al, 1972), Mutu Cl 179 (Gregory et al, 1990), Mutu Cl 148 (Gregory et al, 1990) and Jijoye (Hinuma et al, 1967) were originally derived from Burkitt's lymphomas. LCL#3 (Sinclair et al, 1994), B95-8PF (Farrell et al, 1991) and IB4 (King et al, 1980) were established by immortalization of primary B-cells with the B95-8 strain of EBV.…”

Section: Cell Culturementioning

confidence: 99%

Loss of functional pRB is not a ubiquitous feature of B-cell malignancies

Sinclair

Frost

1999

Br J Cancer

View full text Add to dashboard Cite

Summary Human cancers frequently sustain genetic mutations that alter the function of their G1 cell cycle control check point. These include changes to the retinoblastoma gene and to the genes that regulate its phosphorylation, such as the cyclin-dependent kinase inhibitor p16 INK4a . Altered expression of retinoblastoma protein (pRb) is associated with non-Hodgkin's lymphoma, particularly centroblastic and Burkitt's lymphomas. pRb is expressed in normal B-cells and its regulatory phosphorylation pathway is activated in response to a variety of stimuli. Since human B-lymphoma-derived cell lines are often used as in vitro model systems to analyse the downstream effects of signal transduction, we examined the functional status of pRb in a panel of human B-cell lines. We identified eleven cell lines which express the hyperphosphorylated forms of pRb. Furthermore, we suggest that the pRb protein appears to be functional in these cell lines.

show abstract

Establishment in continuous culture of a new type of lymphocyte from a “burkitt‐like” malignant lymphoma (line d.g.‐75)

Cited by 261 publications

References 32 publications

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Constitutive Activation of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Gene Transcription by IRF1 and IRF2 during Restricted EBV Latency

Epstein-Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF-κB activation

Loss of functional pRB is not a ubiquitous feature of B-cell malignancies

Contact Info

Product

Resources

About