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Molecular Structure and Function of a Novel Immunoinhibitory Protein Institute of Immunological Science

新型免疫抑制蛋白的分子结构与功能中国科学院免疫科学研究所

基本信息

批准号：
63480164
负责人：
SUGIMURA Kazuhisa
金额：
$ 4.22万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480164/
关键词：
Lymphocyte Blastogenesis Inhibitory Factor Mycoplasma Arginine Arginine Deiminase Gene Arginine Metabolism Autoimmune Disease MRL Mice Hyperactive B Lymphocytes LBIF LBIF遺伝子細胞内情報伝達機構サイトカイン細胞増殖細胞周期 IL-2レセプター U937 増殖抑制免疫

项目摘要

In 1987, we identified a cell growth inhibitor, Iymphocyte blastogenesis inhibitory factor (LBIF) in the culture supernatant of a human histiocytic lymphoma, U937. In this study, we have attempted to clarify the molecular structure and function of LBIF. Results are summarized below.1. It has been shown that LBIF is an arginine deiminase (EC 3.5.3.6) originated from Mycoplasma arginine, infecting U937 cells.2. The nucleotide sequence of full-length cDNA clone encoding LBIF has been determined.In a next series of functional analyses of LBIF, we have examined the effects of LBIF on the antibody production of autoimmune MRL mice in vitro.3. It was demonstrated that the IgG antibody production was not inhibited by LBIF in spite of strong inhibition of IgA and IgM antibody production. These results were confirmed by culturing B cells in arginine-free medium supplemented with varying doses of urea cycle metabolities.4. Thus, we demonstrated that gamma-committed B lymphocytes (B gamma) of MRL … More mice selectively expressed the highly elevated Lーarginine syntyhesis while mu or alpha-committed B lymphocyted showed the normal level.5. Normal murine lymphocytes are hardly able to utilize Lーcitrulline to grow and numal lymphocytes are not able to use Lーcitrulline at all.Important implication of our findings are as follows and this abnormality sufficiently explain four important questions of systemic autoimmune disease, such as, (1), predominant propagation of gamma^+ cells, (2), predominant IgG production, (3), disease progression with aging and (4), drastic effects of dietary restriction on the disease manifestation.Autoimmune diseases so far, tend to be considered on the basis of clonal selection (tolerance) or cytokine-responsiveness. This study strongly suggests that systemic autoimmune diseases should be reevaluated as metabolic disorders occurred in lymphocytes, whereas organ-specific autoimmune diseases may belong to immunological disorders with the abnormality of clonal selection. Thus, this study presents a novel perspective on the molecular mechanism of systemic autoimmune disease. Less

1987年，我们在人组织细胞淋巴瘤U937的培养上清液中发现了一种细胞生长抑制因子，即淋巴细胞增殖抑制因子(LBIF)。在本研究中，我们试图阐明LBIF的分子结构和功能。研究结果总结如下：1.研究表明，LBIF是一种精氨酸脱亚胺酶(EC 3.5.3.6)，来源于支原体精氨酸，可感染U937细胞。测定了编码Lbif的全长cDNA克隆的核苷酸序列，在接下来的一系列Lbif的功能分析中，我们检测了Lbif对自身免疫性MRL小鼠体外抗体产生的影响。结果表明，LBIF对IgA和IgM抗体的产生有较强的抑制作用，但对抗体的产生无明显抑制作用。在添加不同剂量尿素循环代谢物的无精氨酸培养液中培养B细胞，证实了上述结果。因此，我们证明了MRL…的伽马承诺B淋巴细胞(B伽马)更多的小鼠选择性地表达高水平的Lー精氨酸联会，而MU或阿尔法承诺的B淋巴细胞则显示正常水平。正常小鼠淋巴细胞几乎不能利用Lー瓜氨酸生长，数量淋巴细胞根本不能利用Lー瓜氨酸。我们的发现的重要意义如下，这一异常充分解释了系统性自身免疫病的四个重要问题，如：(1)γ~+细胞的优势增殖；(2)优势免疫球蛋白的产生；(3)疾病随年龄增长的进展；(4)饮食限制对疾病表现的严重影响。这项研究强烈建议，系统性自身免疫性疾病应重新评估为发生在淋巴细胞内的代谢紊乱，而器官特异性自身免疫性疾病可能属于具有克隆选择异常的免疫紊乱。因此，本研究为研究系统性自身免疫性疾病的分子机制提供了一个新的视角。较少