We have found that a neoplastic Lyl+ B cell clone (BCL1-3B3) can be stimulated to secrete IgM by a Th1-derived cytokine, IL-2, and/or by a Th2-derived cytokine, IL-5. At suboptimal concentrations these interleukins acted synergistically to enhance IgM secretion. Both IL-2 and IL-5 induced increases in βS and J chain mRNA levels. In the presence of both IL, increases in μS and J china mRNA were additive and paralleled increases in IgM secretion. Using cells synchronized at the G1/S border with excess thymidine or in early G1 using isoleicine-deficient media, IL-2 and IL-5 differed in their cell-cycle dependency for signal transmission. IL-5 appeared to act preferentially in late G1 of the cell cycle. In contrast, IL-2 stimulated S and G2 phase cells slightly more efficiently than cells in G1 of the cell cycle. Furthermore, a twofold increase in high-affinity IL-2R was observed as the cells entered S phase. The results suggest that although IL-2 and IL-5 can independently and additively induce differentiation of the Lyl+ BCL1-3B3 cells, they differ in their point of action during the cell cycle. © 1991.