title: ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis.
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.
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Iijima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Masashi
authors.initials: M
authors.lastname: Miharu
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Imadome
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyagawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Akimoto
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakazawa
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
mesh_terms: D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008297:Male; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology*; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology*
chemical_list: D018951:Antigens, CD20; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53