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

• Published in: European journal of immunology Vol. 42; no. 12; pp. 3405 - 3415
• Main Authors: Iijima, Kazutoshi, Yamada, Hiroyuki, Miharu, Masashi, Imadome, Ken‐Ichi, Miyagawa, Yoshitaka, Akimoto, Shingo, Kobayashi, Kenichiro, Okita, Hajime, Nakazawa, Atsuko, Fujiwara, Shigeyoshi, Fujimoto, Junichiro, Kiyokawa, Nobutaka
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.12.2012
• Subjects: Antigens, CD20 - genetics; Antigens, CD20 - immunology; Apoptosis; Apoptosis - genetics; Apoptosis - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B‐cell development; Cell Line; Cell survival; Cells; DNA repair mechanisms; Female; Gene Deletion; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Germinal Center - immunology; Germinal Center - metabolism; Humans; Immune system; Lymphoid organs; Male; Proteins; Transcriptional Activation - genetics; Transcriptional Activation - immunology; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - immunology; Zinc Fingers - genetics; Zinc Fingers - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242530

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.