B Cell Receptor-ERK1/2 Signal Cancels PAX5-Dependent Repression of BLIMP1 through PAX5 Phosphorylation: A Mechanism of Antigen-Triggering Plasma Cell Differentiation
Copyright policy )B Cell Receptor-ERK1/2 Signal Cancels PAX5-Dependent Repression of BLIMP1 through PAX5 Phosphorylation: A Mechanism of Antigen-Triggering Plasma Cell Differentiation
Abstract Plasma cell differentiation is initiated by Ag stimulation of BCR. Until BCR stimulation, B lymphocyte-induced maturation protein 1 (BLIMP1), a master regulator of plasma cell differentiation, is suppressed by PAX5, which is a key transcriptional repressor for maintaining B cell identity. After BCR stimulation, upregulation of BLIMP1 and subsequent suppression of PAX5 by BLIMP1 are observed and thought to be the trigger of plasma cell differentiation; however, the trigger that derepresses BLIMP1 expression is yet to be revealed. In this study, we demonstrated PAX5 phosphorylation by ERK1/2, the main component of the BCR signal. Transcriptional repression on BLIMP1 promoter by PAX5 was canceled by PAX5 phosphorylation. BCR stimulation induced ERK1/2 activation, phosphorylation of endogenous PAX5, and upregulation of BLIMP1 mRNA expression in B cells. These phenomena were inhibited by MEK1 inhibitor or the phosphorylation-defective mutation of PAX5. These data imply that PAX5 phosphorylation by the BCR signal is the initial event in plasma cell differentiation.
- Nagoya University Japan
- Otsuka Pharmaceutical Indonesia
Mice, Inbred BALB C, Lymphoma, MAP Kinase Signaling System, Immunoblotting, Plasma Cells, PAX5 Transcription Factor, Fluorescent Antibody Technique, Receptors, Antigen, B-Cell, Cell Differentiation, Electrophoretic Mobility Shift Assay, Lymphocyte Activation, Real-Time Polymerase Chain Reaction, Transfection, Repressor Proteins, Mice, Animals, Humans, Positive Regulatory Domain I-Binding Factor 1, Phosphorylation, Cells, Cultured
Mice, Inbred BALB C, Lymphoma, MAP Kinase Signaling System, Immunoblotting, Plasma Cells, PAX5 Transcription Factor, Fluorescent Antibody Technique, Receptors, Antigen, B-Cell, Cell Differentiation, Electrophoretic Mobility Shift Assay, Lymphocyte Activation, Real-Time Polymerase Chain Reaction, Transfection, Repressor Proteins, Mice, Animals, Humans, Positive Regulatory Domain I-Binding Factor 1, Phosphorylation, Cells, Cultured
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