Transcription of protooncogenes during stimulation of normal human B lymphocytes

Smeland, Erlend B.; Blomhoff, Heidi Kiil; Ohlsson, Rolf; Davies, Catharina De Lane; Funderud, Steinar; Boye, Erik

doi:10.1002/eji.1830181131

Cited by 14 publications

(7 citation statements)

References 43 publications

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“…Our data suggest an important amplification role of 1176 in IgE synthesis induced by IL-4 and CD40 engagement . Interestingly, both IL4 and anti-CD40 mAb induced 11,6 production in B cells (9,11) . Furthermore, IL6 increases the phosphorylation of CD40 in human B cells, thus leading to a CD40-IL6 loop (9) .…”

Section: Resultsmentioning

confidence: 99%

CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells.

Jabara

Geha

et al. 1990

The Journal of Experimental Medicine

429

183

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A novel pathway of IgE-B cell differentiation has been identified. Engagement of the B cell antigen CD40 by F(ab')2 fragments of monoclonal antibody (mAb) 626.1 in the presence of recombinant interleukin 4 (rIL-4) induced intense IgE synthesis, but modest IgG synthesis, by highly purified human B cells. Surface IgE- B cells isolated by cell sorting were induced to produce IgE by mAb 626.1 and IL-4. Thus, IgE synthesis is unlikely to result from expansion of a B cell population precommitted to IgE in vivo. A neutralizing anti-IL-6 antibody strongly, but not completely, inhibited the IgE response. This indicates that autocrine production of IL-6 plays an important amplification role in IgE synthesis triggered by anti-CD40 mAb and IL-4. Although the exact role played by CD40 in IgE responses in vivo remains to be established, this T cell-independent system represents a useful model to characterize the biochemical and molecular events leading to IgE synthesis in human B cells.

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Section: Resultsmentioning

confidence: 99%

CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells.

Jabara

Geha

et al. 1990

The Journal of Experimental Medicine

429

183

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“…during development (Ohlsson et al, 1981; L.Holmgren, R.Glaser, S.Pfeifer-Ohlsson and R.Ohlsson, in preparation). However, in comparison to many genes, which are regulated in a strictly limited cell type-specific manner via enhancer elements, the c-sis gene is expressed by a wide range of cell lineages, although this occurs in very specific spatial and temporal 'windows' for these cell types Smeland et al, 1988;Ohlsson et al, 1991). For this reason, it is perhaps not surprising that the control mechanisms involved in the regulation of c-sis expression appear more complex and diverse than those associated with genes which are more strictly and simply limited to a specific cell type (or types).…”

Section: Discussionmentioning

confidence: 99%

Expression of the human PDGF-B gene is regulated by both positively and negatively acting cell type-specific regulatory elements located in the first intron.

et al. 1991

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Potential cis‐acting regulatory elements of the human platelet derived growth factor‐B (PDGF‐B) gene were identified by DNase I hypersensitive site mapping. The transcription unit was examined for the presence of hypersensitive sites in chromatin DNA isolated from human term placental cytotrophoblasts, human placental fibroblasts, the JEG‐3 choriocarcinoma cell line and the U2‐OS osteosarcoma cell line. A number of cell type‐specific hypersensitive sites were identified, all within the 1st intron. Transient transfection of JEG‐3 cells with CAT constructs containing regions of the c‐sis 1st intron linked to the basal c‐sis promoter identified a cell type‐specific positive regulatory activity within the intron, composed of at least two distinct elements. One element appeared to be specific for JEG‐3 cells, while the other was also active in U2‐OS cells. The overall positive regulatory activity of the 1st intron region was specific for JEG‐3 cells, but did not function as a classically defined enhancer, as it was orientation‐dependent (unless stably integrated into chromatin DNA). In addition, the activator appears to require interaction with the c‐sis promoter, as little or no activation was seen when either the SV40 or human beta‐globin promoters were substituted for the c‐sis promoter. The 1st intron also contained a negative regulatory element, which was specific for U2‐OS cells and silenced an abnormally high basal c‐sis promoter activity in these cells. The complexity of the transcriptional control of the PDGF‐B gene is discussed.

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“…G-loop formation will prolong denaturation of the DNA duplex, and thereby increase the probability of AID attack. Like the S regions, c-MYC is transcribed upon B-cell activation (Cole, 1986;Smeland et al, 1988); and it contains distinctly G-rich regions on the nontemplate DNA strand. This suggested that structures might form within the transcribed c-MYC gene and promote interactions with AID, thereby contributing to translocation or aberrant hypermutation of c-MYC in germinal center B cells.…”

Section: Introductionmentioning

confidence: 99%

AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation

et al. 2005

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Translocation and aberrant hypermutation of c-MYC are common in B-cell lymphomas. Activation-induced Cytidine Deaminase (AID) initiates switch recombination and somatic hypermutation in B cells by targeted deamination of transcribed genes. We show that transcription of the immunoglobulin S regions and c-MYC results in formation of similar DNA structures, 'G-loops', which contain a cotranscriptional RNA: DNA hybrid on the C-rich strand and single-stranded regions and G4 DNA on the G-rich strand. AID binds specifically to G-loops within transcribed S regions and c-MYC, and G-loops in c-MYC map to the regions associated with translocation breakpoints and aberrant hypermutation in B-cell lymphomas. Aberrant targeting of AID to DNA structures formed upon c-MYC transcription may therefore contribute to the genetic instability of c-MYC in B-cell malignancies.

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Transcription of protooncogenes during stimulation of normal human B lymphocytes

Cited by 14 publications

References 43 publications

CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells.

CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells.

Expression of the human PDGF-B gene is regulated by both positively and negatively acting cell type-specific regulatory elements located in the first intron.

AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation

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