B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1

Abstract

It was recently shown that T cells, macrophages and fibroblasts produce growth factors for B cell hybridomas and plasmacytomas. These factors were subsequently identified as members of a new family of cytokines on the basis of NH2-terminal amino acid sequence analyses. Using T cell-derived interleukin-HP1 (HP1), purified to homogeneity, as the prototype of this family, we examined the effects of these molecules in conventional polyclonal B cell activation assays with anti-immunoglobulin antibodies or dextran sulfate as co-stimulators. In the absence of other cytokines, the only significant effect of HP1 was to stimulate moderately the proliferation of anti-immunoglobulin-activated B cells. By contrast, in conjunction with interleukin 1, HP1 became a major growth and differentiation factor not only for B cells activated with anti-immunoglobulin antibodies but also for dextran sulfate-stimulated and even for unstimulated B cells. In fact, with respect to cell proliferation or IgM synthesis, the IL 1-HP1 combination proved to be equivalent to B cell stimulatory factors like IL 4 or IL 5. This B cell stimulatory activity was not due to the presence of a contaminant in the HP1 preparation because it was also observed with purified plasmacytoma growth factors derived from macrophages and fibroblasts, and could be inhibited by a monoclonal anti-HP1 antibody.