ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis

Kazutoshi Iijima, Hiroyuki Yamada, Masashi Miharu, Ken Ichi Imadome, Yoshitaka Miyagawa, Shingo Akimoto, Kenichiro Kobayashi, Hajime Okita, Atsuko Nakazawa, Shigeyoshi Fujiwara, Junichiro Fujimoto, Nobutaka Kiyokawa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

We previously identified zinc finger (ZF) protein ZNF385B as a molecule specifically expressed in Burkitt's lymphoma (BL) among hematologic malignancies. Here, we investigated ZNF385B expression in healthy B cells in a variety of hematological tissues by RT-PCR and immunohistochemistry. ZNF385B expression was found to be limited to a subset of GC B cells, the healthy counterpart to BL B cells. To elucidate the function of ZNF385B in healthy B cells, we established a tetracycline-controlled protein-inducible system in B-cell lines and observed that ectopic expression of the longest transcript variant of ZNF385B, possessing four ZF domains, induced upregulation of PERP and FAS/CD95, a downstream target of p53, and activation of caspase, resulting in apoptosis induction. However, a ZNF385B deletion mutant with three ZF domains corresponding to shorter isoforms, did not induce upregulation; rather it inhibited apoptosis induced by CD20 cross-linking and BCR stimulation. The direct binding of ZNF385B with p53 has suggested the involvement of ZNF385B in B-cell apoptosis via modulation of p53 transactivation; our data indicate that ZNF385B characteristically expressed in GC B cells has both proapoptotic and antiapoptotic activities depending on the type of isoform and should be a novel player in GC B-cell selection.

Original languageEnglish
Pages (from-to)3405-3415
Number of pages11
JournalEuropean Journal of Immunology
Volume42
Issue number12
DOIs
Publication statusPublished - 2012 Dec
Externally publishedYes

Keywords

  • Apoptosis
  • B-cell development
  • Cell survival
  • DNA repair mechanisms
  • Lymphoid organs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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