Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.
Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.
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DOI：
10.1084/jem.181.4.1539
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发表时间：
1995-04-01
期刊：
影响因子：
--
通讯作者：
Uhr JW
中科院分区：
文献类型：
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作者：
Racila E;Scheuermann RH;Picker LJ;Yefenof E;Tucker T;Chang W;Marches R;Street NE;Vitetta ES;Uhr JW
在肿瘤细胞攻击前用肿瘤免疫球蛋白(Ig)免疫BALB/c小鼠，可诱导小鼠B细胞淋巴瘤(BCL1)发生肿瘤休眠。在这份报告中，我们研究了诱导休眠的免疫学和细胞学机制。将BCL1肿瘤细胞注射到被动免疫的SCID小鼠体内，免疫小鼠分别免疫独特型(ID)免疫T淋巴细胞和非独特型(ID)免疫T淋巴细胞。结果表明，抗IgM抗体足以诱导小鼠进入休眠状态。抗IGD和CD44(Pgp1)等细胞表面分子的抗体对肿瘤生长无影响。ID免疫T细胞本身对SCID小鼠的肿瘤生长也没有影响。然而，同时转移抗ID和ID免疫的T细胞增强了休眠状态的诱导和持续时间。体外研究表明，抗IgM抗体可在数小时内诱导细胞凋亡，并可使细胞周期停滞24小时，超交联可促进细胞凋亡。Fc-γRII受体在负性信号转导中的作用很小或没有作用。在体外没有负面信号的抗体在体内不会诱导休眠。结果提示，抗-IgM通过作为IgM介导的信号转导通路的激动剂，在诱导肿瘤对BCL1的休眠中起决定性作用。
Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.