B cell receptor-ERK1/2 signal cancels PAX5-dependent repression of BLIMP1 through PAX5 phosphorylation: A mechanism of antigen-triggering plasma cell differentiation

Takahiko Yasuda, Fumihiko Hayakawa, Shingo Kurahashi, Keiki Sugimoto, Yosuke Minami, Akihiro Tomita, Tomoki Naoe

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6127-6134
Number of pages8
JournalJournal of Immunology
Volume188
Issue number12
DOIs
Publication statusPublished - 15-06-2012

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Plasma Cells
Cell Differentiation
B-Lymphocytes
Phosphorylation
Antigens
Proteins
Up-Regulation
Messenger RNA
Mutation

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Yasuda, Takahiko ; Hayakawa, Fumihiko ; Kurahashi, Shingo ; Sugimoto, Keiki ; Minami, Yosuke ; Tomita, Akihiro ; Naoe, Tomoki. / B cell receptor-ERK1/2 signal cancels PAX5-dependent repression of BLIMP1 through PAX5 phosphorylation : A mechanism of antigen-triggering plasma cell differentiation. In: Journal of Immunology. 2012 ; Vol. 188, No. 12. pp. 6127-6134.
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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.",
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B cell receptor-ERK1/2 signal cancels PAX5-dependent repression of BLIMP1 through PAX5 phosphorylation : A mechanism of antigen-triggering plasma cell differentiation. / Yasuda, Takahiko; Hayakawa, Fumihiko; Kurahashi, Shingo; Sugimoto, Keiki; Minami, Yosuke; Tomita, Akihiro; Naoe, Tomoki.

In: Journal of Immunology, Vol. 188, No. 12, 15.06.2012, p. 6127-6134.

Research output: Contribution to journalArticle

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