Episomal vectors to monitor and induce somatic hypermutation in human Burkitt-Lymphoma cell lines

Rückerl, Florian; Busse, Birgit; Brinckmann, Jürgen

doi:10.1016/j.molimm.2005.09.011

Cited by 13 publications

(10 citation statements)

References 34 publications

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“…Hypermutation on this reporter is increased by Igk enhancer elements that have earlier been shown to confer Ig locus control (Polack et al, 1993). The reporter used differs from an earlier published system that has been developed and confirmed to measure somatic hypermutation in human cells (Ruckerl et al, 2006) by an improved SV40-promoter-driven hygromycin resistance cassette allowing its application to more cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…The promoter in front of the hygromycin resistance gene in the published pEpi hypermutation reporter (Ruckerl et al, 2006) was exchanged for a SV40 promoter using the SgrA1 and Cpo1 restriction sites in pEpi and pBB230. For cloning of the shRNA vectors, the corresponding F and R oligonucleotides (see Table 2) were annealed and cloned into the pBJ3*-PincU6-ngfr vector cut with Pml1 and Xho1.…”

Section: Vectorsmentioning

confidence: 99%

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c-Myc overexpression promotes a germinal center-like program in Burkitt's lymphoma

et al. 2009

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The germinal center (GC) reaction has a pivotal function in human B-cell lymphomagenesis. Genetic aberrations occurring during somatic hypermutation and class switch recombination deregulate key factors controlling B-cell physiology and proliferation. Several human lymphoma entities are characterized by a constitutive GC phenotype and ongoing somatic hypermutation, but the molecular basis for this phenomenon is only partly understood. We have investigated the reasons for a constitutive GC-like program in Burkitt's lymphoma cells. Here, overexpression of c-Myc leads to a centroblast phenotype, promotes high constitutive expression of the key GC factors Bcl-6, E2A and activation-induced cytidine deaminase and contributes to proliferation and somatic hypermutation. Our findings elucidate how the activity of a pivotal transcription factor may freeze B-cell lymphoma cells in a constitutive GC-like state that is even maintained at an extrafollicular location.

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Section: Resultsmentioning

confidence: 99%

Section: Vectorsmentioning

confidence: 99%

c-Myc overexpression promotes a germinal center-like program in Burkitt's lymphoma

et al. 2009

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“…Ubiquitous overexpression of AID in a transgenic mouse results in T cell lymphoma (33). However, expression of AID in certain human lymphoma B cell lines was associated with hypermutation of Ig sequences (34,35). The pathogenic role of AID has not been widely studied in human autoimmune disease because the AID gene is mainly expressed by GC B cells and is down-modulated in circulating plasma and memory B cells (36).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Activation-Induced Cytidine Deaminase in B Cells Is Associated with Production of Highly Pathogenic Autoantibodies

Hsu

Yang

et al. 2007

The Journal of Immunology

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Defective receptor editing or defective B cell checkpoints have been associated with increased frequency of multireactive autoantibodies in autoimmune disease. However, Ig somatic hypermutation and/or class switch recombination may be mechanisms enabling the development of pathogenic multireactive autoantibodies. In this study, we report that, in the BXD2 mouse model of autoimmune disease, elevated expression of activation-induced cytidine deaminase (AID) in recirculating follicular CD86+ subsets of B cells and increased germinal center B cell activity are associated with the production of pathogenic multireactive autoantibodies. CD4 T cells from BXD2 mice that expressed increased levels of CD28 and an increased proliferative response to anti-CD3 and anti-CD28 stimulation are required for this process. Inhibition of the CD28-CD86 interaction in BXD2 mice with AdCTLA4-Ig resulted in normalization of AID in the B cells and suppression of IgG autoantibodies. This treatment also prevented the development of germinal center autoantibody-producing B cells, suggesting that an optimal microenvironment enabling AID function is important for the formation of pathogenic autoantibodies. Taken together, our data indicate that AID expression in B cells is a promising therapeutic target for the treatment of autoimmune diseases and that suppression of this gene may be a molecular target of CTLA4-Ig therapy.

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“…32 After transfection of the vector into the hypermutating EBV-positive Burkitt lymphoma cell line Raji, a steady increase in the relative frequency of GFP expressing cells was detectable, indicating ongoing somatic hypermutation (Fig. 1A).…”

Section: Effect Of Chk2 Inhibition On Somatic Hypermutation In Human mentioning

confidence: 96%

Checkpoint kinase 2 is required for efficient immunoglobulin diversification

et al. 2014

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Episomal vectors to monitor and induce somatic hypermutation in human Burkitt-Lymphoma cell lines

Cited by 13 publications

References 34 publications

c-Myc overexpression promotes a germinal center-like program in Burkitt's lymphoma

c-Myc overexpression promotes a germinal center-like program in Burkitt's lymphoma

Overexpression of Activation-Induced Cytidine Deaminase in B Cells Is Associated with Production of Highly Pathogenic Autoantibodies

Checkpoint kinase 2 is required for efficient immunoglobulin diversification

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