Critical role of Pcid2 in B cell survival through the regulation of MAD2 expression

Teruo Nakaya, Kazuhiko Kuwahara, Kazutaka Ohta, Masahiro Kitabatake, Teppei Toda, Naoki Takeda, Tokio Tani, Eisaku Kondo, Nobuo Sakaguchi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The mitotic checkpoint is essential for maintaining genomic stability in differentiating B cells undergoing genetic alterations of the Ig gene. In this study, using real-time RT-PCR and in situ RNA hybridization, we demonstrated that MAD2 mRNA export is selectively regulated by Pcid2/Thp1. Pcid2 small interfering RNA induced a cell-cycle abnormality with increased apoptosis and polyploidy, as previously observed in MAD2-knockdown cells. Pcid2 small interfering RNA reduced MAD2 expression, but not the expression of other cell-cycle checkpoint proteins, such as MAD1 and BUBR1, or the cell-cycle-associated proteins, cyclin A, cyclin B1, and cyclin-dependent kinase 1. In mouse B lineage cells, Pcid2 transcripts appeared in a stage-dependent manner at high levels in bone marrow pre-B and immature B cells, and in spleen transitional 1 and follicular B cells, but at lower levels in pro-B, transitional 2, and marginal zone B cells, suggesting a stage-dependent requirement for MAD2 regulation. Cd19-cre-derived targeting of the Pcid2 gene induced a mature B cell deficiency in mice. These findings indicate that Pcid2 is essential for B cell survival through the regulation of MAD2 expression during B cell differentiation.

Original languageEnglish
Pages (from-to)5180-5187
Number of pages8
JournalJournal of Immunology
Volume185
Issue number9
DOIs
Publication statusPublished - 01-11-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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