川崎医科大学 教員情報

クリバヤシ　フトシ   Futoshi Kuribayashi   栗林　太    所属   川崎医科大学  医学部 基礎医学　生化学    職種   教授
論文種別	原著
単著／共著の別	共著
言語種別	英語
査読の有無	査読あり
表題	Possible involvement of Helios in controlling the immature B cell functions via transcriptional regulation of protein kinase Cs
掲載誌名	正式名：Results in Immunology
巻・号・頁	1(1),88–94頁
著者・共著者	Hidehiko Kikuchi, Masami Nakayama, Yasunari Takami, Futoshi Kuribayashi, Tatsuo Nakayama
発行年月	2011/05
概要	The transcription factor Ikaros family consists of five zinc-finger proteins: Ikaros, Aiolos, Helios, Eos and Pegasus; these proteins except Pegasus are essential for development and differentiation of lymphocytes. However, in B lymphocytes, the physiological role of Helios remains to be elucidated yet, because its expression level is very low. Here, we generated the Helios-deficient DT40 cells, Helios−/−, and showed that the Helios-deficiency caused significant increases in transcriptions of four protein kinase Cs (PKCs); PKC-δ, PKC-ε, PKC-η and PKC-ζ, whereas their expressions were drastically down-regulated in the Aiolos-deficient DT40 cells, Aiolos−/−. In addition, Helios−/− was remarkably resistant against phorbol 12-myristate 13-acetate (PMA)/ionomycin treatment, which mimics the B cell receptor (BCR)-mediated stimulation. In the presence of PMA/ionomycin, their viability was remarkably higher than that of DT40, and their DNA fragmentation was less severe than that of DT40 in the opposite manner for the Aiolos-deficiency. The resistance against the PMA/ionomycin-induced apoptosis of Helios−/− was sensitive to Rottlerin but not to Go6976. In addition, the Helios-deficiency caused remarkable up-regulation of the Rottlerin-sensitive superoxide (O2−)-generating activity. These data suggest that Helios may contribute to the regulation of the BCR-mediated apoptosis and O2−-generating activity, via transcriptional regulation of these four PKCs (especially PKC-δ) in immature B lymphocytes. Together with previous data, our findings may significantly help in the understanding of the B lymphocyte-specific expressions of PKC genes and molecular mechanisms of both the BCR-mediated apoptosis involved in negative selection and the O2−-generating system in immature B lymphocytes.