Cutting edge:: The development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor α, and Th2 cells

Although IL-4-producing B cells (B effector 2 cells) are found following infection and immunization, the signals regulating IL-4 production by Be2 cells are unknown. We show that culturing naive B cells with Th2 cells induces, up-regulation of IL-4 in the B cells with a concomitant down-regulation of T-bet, IL-12R beta 2, and IFN-gamma. Upregulation of IL-4 in the Be2 cells is dependent on both T cells and IL-4 as IL-4R alpha-deficient B cells primed with Th2 cells did not transcribe IL-4 and B cells primed in the presence of IL-4-deficient Th2 cells produced IFN-gamma instead of IL-4. Likewise, the in vivo development of IL-4-expressing B cells in a nematode infection model was dependent on both T cells and IL-4R alpha-mediated signals. Thus, the differentiation of naive B cells into IL-4-expressing Be2 cells is regulated by a combination of T cell-dependent signals and the cytokine environment and this process is critically dependent upon the IL-4/IL-4R signaling pathway.