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ERKs Induce Expression of the Transcriptional Repressor Blimp-1 and Subsequent Plasma Cell Differentiation. (Prof. Kurosaki in Science Signal.)
In immune cells, the positive role of the extracellular signal?regulated kinase (ERK) signaling pathway in cell cycle progression and survival is well established; however, it is unclear whether ERK signaling plays a role in cell differentiation.
The authors report that ERKs are essential for the differentiation of B cells into antibody-producing plasma cells and that ERKs induce the expression of Prdm1, which encodes Blimp-1, a transcriptional repressor and "master regulator" of plasma cell differentiation. Transgenic mice with conditional deletion of both ERK1 and ERK2 in germinal center (GC) B cells lacked plasma cells differentiated after GC formation, and memory B cells from these mice failed to differentiate into plasma cells.
In addition, ERK1- and ERK2-deficient B cells exhibited impaired Prdm1 expression upon stimulation with antibody against CD40 in the presence of interleukin-4; conversely, enforced expression of Prdm1 in ERK1- and ERK2-deficient B cells restored the generation of plasma cells. Thus, the study suggests that cytokines stimulate ERKs to induce the production of Blimp-1 and that ERKs thereby contribute to the process of cellular differentiation.
Laboratory for Lymphocyte Differentiation
Immunology Frontier Research Center (IFReC), Osaka University
Research Center for Allergy and Immunology, RIKEN