CHARACTERIZATION OF A NOVEL INTERLEUKIN-6 AUTOCRINE-DEPENDENT HUMAN PLASMA-CELL LINE

A new human monoclonal plasma cell line, designated UTMC-2, was establ ished from the pleural effusion of a patient with immunoglobulin (Ig)A kappa-related multiple myeloma. The cultured cells were Epstein-Barr virus-negative and exhibited the morphological and ultrastructural fea tures characteristic of plasma cells. Immunohistochemical analyses rev ealed the presence of cytoplasmic IgA kappa as well as the plasma cell -associated surface antigens CD38 and GD56. Other B-cell markers, incl uding CD10, CD19, CD2O, and HLA-DR, were absent. The UTMC-2 cells were interleukin (IL)-6 responsive: Co-culture with IL-6 increased IgA kap pa synthesis and cell proliferation in a dose-dependent manner. In con trast, an IL-6 antisense oligonucleotide had an opposite effect. Altho ugh the expressed IL-6 mRNA (as demonstrated by scriptase-polymerase c hain reaction (RT-PCR)) and contained IL-6, the concentration of this cytokine in cell culture supernatants was less than that detectable by the enzyme-linked immunosorbent assay (ELISA) employed (i.e. <3 pg/ml ). Further, cell growth was not inhibited by polyclonal or monoclonal anti-IL-6 antibodies. Flow cytometric analysis revealed that IL-6 rece ptors present on the surface of the UTMC-2 cells were not saturated wi th endogenous IL-6. Taken together, these results indicate that, in th is human plasma cell line, IL-6 functions uniquely in an intracellular autocrine fashion to enhance Ig synthesis and cell growth. In this re spect, the UTMC-2 cells represent a novel resource for further study o f the role of IL-6 in the pathogenesis of multiple myeloma.