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The intracellular pathways that induce the differentiation of naïve B cells into antibody-secreting plasma cells remain poorly defined. A new study now provides surprising evidence that the activation of extracellular signal–regulated kinase (ERK) is pivotal for inducing the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp-1), which is required for plasma cell differentiation. Consequently, ERK-deficient B cells were unable to generate plasma cells effectively. This is an unexpected result, because previous work has shown that ERK signaling functions chiefly to induce cell division, whereas plasma cells are considered to be nondividing, terminally differentiated cells. This finding not only reveals an important signaling pathway that underlies antibody-mediated immunity but also raises important questions about the varying roles that ERK, and perhaps other kinases, may play in different biological contexts.