Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mouse B cell lymphoma 70Z/3 is membrane immunoglobulin M (mIgM) negative, but treatment of the cells with bacterial lipopolysaccharide (LPS) induces the expression of kappa (kappa) light chain synthesis, and the cells become mIgM+. In wild type cells, this reaction is maximal after 24 h; we have isolated a variant, 1B8, which becomes mIgM+ only after a more prolonged incubation with LPS. This delayed response results from a reduced rate of accumulation of (kappa) mRNA and protein. The transcription factor, NF-kappa B is present in the cytoplasm of both the wild type and the variant cells in its inactive form. The delay in kappa expression is correlated with the failure of NF-kappa B to be activated and translocated to the nucleus. Although NF-kappa B cannot be activated by LPS, it can be activated by treatment with phorbol ester (PMA). In contrast to the clear defect in NF-kappa B, LPS treatment of 1B8 cells causes the octamer-binding factor OTF-2 to increase normally. We conclude that the defect in 1B8 cells is in an early part of the LPS activation pathway, prior to the activation of NF-kappa B, but after the signal for OTF-2 induction. The phenotype of 1B8 demonstrates that an increase in OTF-2 alone is sufficient to cause a large increase in kappa transcription in 70Z/3 cells, but that without NF-kappa B, the response is slow to develop. In this view, NF-kappa B functions to facilitate kappa transcription and to speed its rate of increase, but is not required for the long-term response of 70Z/3 cells to LPS.
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PMID:Slow response variant of the B lymphoma 70Z/3 defective in LPS activation of NF-kappa B. 210 8

The kappa immunoglobulin (Igk) light chain locus is transcriptionally silent in the mouse B-cell lymphoma 70Z/3. However, exposure to lipopolysaccharide (LPS) or interferon-gamma (IFN) causes a marked increase in Igk transcription. By immunoselection, we isolated two variants that are nonresponsive to IFN. One variant, AT7.2, has retained its response to LPS (IFN-LPS+), whereas the other, AT3.3, is also nonresponsive to LPS (IFN-LPS-). Stable transfection of an intact Igk gene does not rescue the phenotype of either variant. Both variants have intact Igk genes and neither is deficient in the binding or uptake of IFN. Nuclear extracts from LPS-treated wild-type 70Z/3 cells show strong increases in three transcription factors: OTF-2, NF-kappa B, and kBF-A. Remarkably, when the IFN-LPS- variant is treated with LPS, all three transcription factors are still observed in the nuclear extracts. Treatment of wild-type cells with either LPS or IFN also causes a decrease in nuclear complexes that bind to two other regions of the Igk intron enhancer, the octenh and the E kappa MHCIC regions. Both of these changes are also observed after LPS or IFN treatment of the IFN-LPS- variant. Thus, this variant transduces the IFN and LPS signals at least into the nuclear compartment, but still fails to activate Igk transcription. In contrast, the IFN-LPS+ variant decreases neither the octenh nor the E kappa MHCIC binding complexes in response to IFN. This variant may be defective in transducing the IFN signal to the nucleus. These variants will be useful in studying the activation of Igk transcription and the IFN signaling pathway in B cells.
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PMID:Two different IFN-gamma nonresponsive variants derived from the B-cell lymphoma 70Z/3. 803 28