IL-15 HAS STIMULATORY ACTIVITY FOR THE INDUCTION OF B-CELL PROLIFERATION AND DIFFERENTIATION

The identification and cloning of the novel cytokine IL-15 were recent ly described. IL-15 is produced by a wide range of cell types, with th e highest levels of IL-15 mRNA being detected in epithelial lines, mon ocytes, muscle, and placenta. Although it has no sequence identity wit h IL-2, IL-15 shares many of the T cell-stimulatory activities describ ed for IL-2. We have examined IL-15 for its ability to stimulate B cel ls and have compared its activity with that of IL-2. IL-15 costimulate s proliferation of B cells activated with immobilized anti-human IgM o r phorbol ester, but has no stimulatory effect on resting B cells. In combination with recombinant CD40L, IL-15 is a potent inducer of polyc lonal IgM, IgG1, and IgA secretion, but does not cause production of I gG4 or IgE. The activity of IL-15 in B cell proliferation and differen tiation assays is comparable with that of IL-2. Studies that used neut ralizing Abs have demonstrated that, for signal transduction in B cell s, IL-15 uses the beta-chain of the IL-2R complex but, unlike IL-2, do es not require the alpha-chain. IL-2 is required for the generation of a human primary Ag-specific in vitro response using sheep erythrocyte s as Ag. Of all cytokines examined, only IL-15 has the capacity to rep lace IL-2 in this system, although only partially. In summary, IL-15 h as comparable activity with IL-2 for the induction of B cell prolifera tion and differentiation and uses at least some of the components of t he IL-2R complex to mediate its effects.