Slow response variant of the B lymphoma 70Z/3 defective in LPS activation of NF-?B

Publisher Website
Google Scholar
Abstract
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 (κ) 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 (κ) mRNA and protein. The transcription factor, NF-κB is present in the cytoplasm of both the wild type and the variant cells in its inactive form. The delay in κ expression is correlated with the failure of NF-κB to be activated and translocated to the nucleus. Although NF-κB cannot be activated by LPS, it can be activated by treatment with phorbol ester (PMA). In contrast to the clear defect in NF-κB, 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-κB, 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 κ transcription in 70Z/3 cells, but that without NF-κB, the response is slow to develop. In this view, NF-κB functions to facilitate κ transcription and to speed its rate of increase, but is not required for the long-term response of 70Z/3 cells to LPS.