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 journalArticlepeer-review

25 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
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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