Abstract
Interleukin-6 (IL-6) was originally identified as a B cell differentiation factor that induces final maturation of activated B cells into antibody-producing plasma cells. It is now known that IL-6 is a multifunctional cytokine that is produced by a wide range of cells and suggested to play important roles in host defense mechanisms.
Recently, it has been suggested that deregulated expression of IL-6 is associated with the pathogenesis of plasma cell neoplasias. The growth factor for murine hybridoma/plasmacytoma was found to be identical to IL-6. Furthermore, IL-6 was shown to be a growth factor for human myeloma cells.
To clarify how IL-6 plays a role in the generation of plasma cell neoplasias, transgenic mice were produced by introducing the human IL-6 gene.
IL-6 transgenic mice of C57BL/6 origin developed massive polyclonal IgGi plasmacytosis, but not plasmacytomas. However, introduction of BALB/c genetic background into IL-6 transgenic mice was found to induce malignant transformation of plasma cells in about 1/3 of transgenic mice. These plasmacytoma cells were shown to be IgA plasmacytoma cells and contain the chromosomal translocation t (12; 15), which is common in pristane-induced plasmacytomas in BALB/c mice and is thought to induce the c-myc gene rearrangement.
These data demonstrated that overexpression of the IL-6 gene could induce plasma cell neo-plasias through a polyclonal plasmacytosis in concert with a certain BALB/c genetic background.
