2 DIFFERENT IFN-GAMMA NONRESPONSIVE VARIANTS DERIVED FROM THE B-CELL LYMPHOMA-7OZ 3/

The kappa immunoglobulin (Igk) light chain locus is transcriptionally silent in the mouse B-cell lymphoma 70Z/3. However, exposure to lipopo lysaccharide (LPS) or interferon-gamma(IFN) causes a marked increase i n Igk transcription. By immunoselection, we isolated two variants that are nonresponsive to IFN. One variant, AT7.2, has retained its respon se to LPS (IFN-LPS(+)), whereas the other, AT3.3, is also nonresponsiv e to LPS (IFN-LPS-). Stable transfection of an intact Igk gene does no t rescue the phenotype of either variant. Both variants have intact Ig k genes and neither is deficient in the binding or uptake of IFN. Nucl ear extracts from LPS-treated wild-type 70Z/3 cells show strong increa ses in three transcription factors: OTF-2, NF-kappa B, and kBF-A. Rema rkably, when the IFN-LPS- variant is treated with LPS, all three trans cription factors are still observed in the nuclear extracts. Treatment of wild type cells with either LPS or IFN also causes a decrease in n uclear complexes that bind to two other regions of the Igk intron enha ncer, the OCt(enh) and the E kappa MHCIC regions. Both of these change s 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(+) vt decreases neither the OCt(enh) nor th e E kappa MHCIC binding complexes in response to IFN. This variant may be defective in transducing the IFN signal to the nucleus. These vari ants will be useful in studying the activation of Igk transcription an d the IFN signaling pathway in B cells.