INTERLEUKIN-5 (IL-5) AND IL-6 DEFINE 2 MOLECULARLY DISTINCT PATHWAYS OF B-CELL DIFFERENTIATION

Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete a ntibody. However, it has not been possible to directly compare the eff ects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We have identified a clonal, indu cible B-cell lymphoma, CH12, that has this property. Both IL-5 and IL- 6 can independently stimulate increases in steady-state levels of immu noglobulin and J-chain mRNA and proteins, and they both induce the dif ferentiation of CH12 into high-rate antibody-secreting cells. Neverthe less, there are significant differences in the activities of these two lymphokines. First, while IL,6 acts only as a differentiation factor, IL-5 also augments the proliferation of CH12 cells. Second, the diffe rentiation stimulated by IL-5 but not by IL-6 is partially inhibited b y IL-4. Inhibition of IL-5-induced differentiation was not at the leve l of IL-5 receptor expression, since IL-4 did not inhibit IL-5-induced proliferation. Third, IL-5 but not IL-6 stimulated increased mouse ma mmary tumor proviral gene expression in CH12 cells. These results demo nstrate that while both IL-5 and IL-6 may act as differentiation facto rs for B cells, they induce differentiation by using at least partiall y distinct molecular pathways. Our results also establish that B cells characteristic of a single stage of development can independently res pond to IL-4, IL-5, and IL-6.