Purified recombinant human leukocyte interferons IFLrA and IFLrD induce human lupus inclusions in Raji and Daudi...

Raji and Daudi are human B lymphoblastoid cell lines that readily form lupus inclusions (LIs; TRS) when grown in medium supplemented with leukocyte-, or fibroblast-derived interferon (IFN-alpha, -beta, respectively). WISH, MDBK, and GM2504 are three cell lines commonly used to measure antiviral activities. None of them form LIs in their antiviral response to alpha or immune (gamma)IFN. This distinguishes between the abilities of a cell to develop an antiviral state and to form LIs in response to IFN. Human (Hu) lymphoblastoid IFN and the two pure and homogeneous recombinant human IFN-alpha proteins IFLrA and IFLrD induce LIs in Raji cells and Daudi cells. In Daudi, a simultaneous inhibition of cell growth occurs. When compared by antiviral activities, IFLrA inhibits the growth of Daudi cells more, while IFLrD induces the greater frequency of LIs. According to molecular concentration, IFLrA and IFLrD at 133 X 10(-13) M induce LIs in Daudi cells to their maximum frequency. Growth inhibition for these same cell samples is also at maximum for IFLrA, but only 25% of maximum for IFLrD. Our results with Raji and Daudi cells provide evidence against a cause-and-effect relationship between these two biologic responses to IFN by Daudi cells. They also provide evidence for distinct, but interacting, intracellular pathways. This phenomenon is a new explanation for some of the biologic diversity shown for the HuIFNs-alpha.