Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma
Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma
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DOI：
10.1038/sj.leu.2403244
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发表时间：
2004-03-01
期刊：
影响因子：
11.4
通讯作者：
Raveche, E
中科院分区：
文献类型：
--
作者：
Czarneski, J;Lin, YC;Raveche, E
新西兰B小鼠发生B细胞亚群（B-1细胞）的年龄相关恶性扩增，并自分泌产生IL-10。IL-10是一种具有抗炎特性的多效性细胞因子，是恶性B细胞的有效生长和存活因子。为了进一步研究在NZ B小鼠中恶性B-1克隆的发展和扩增中对IL-10的体内需求，我们在NZ B背景下开发了一种纯合IL-10敲除（KO）小鼠品系。NZ B IL-10 KO小鼠产生腹膜B-1细胞的频率与杂合和野生型同窝小鼠大致相同。相反，在野生型NZ B中观察到的外周血和脾脏中恶性B-1细胞的发展很少发生在NZ B IL-10 KO中。脾B细胞表面标志物表达的表型分析表明，与恶性B-1脾淋巴瘤的NZ B细胞相反，NZ B IL-10 KO脾B细胞表面标志物表达表明大多数B细胞是典型的B-2细胞。在缺乏IL-10的情况下，自发活化的B细胞和抗凋亡基因表达减少，淋巴瘤发病率降低。这些结果表明，IL-10是这种B细胞恶性疾病进展的关键因素。
NZB mice develop an age-related malignant expansion of a subset of B cells, B-1 cells, with autocrine production of IL-10. IL-10, a pleiotropic cytokine with anti-inflammatory properties, is a potent growth and survival factor for malignant B cells. To further examine the in vivo requirement for IL-10 in the development and expansion of malignant B-1 clones in NZB mice, we developed a strain of homozygous IL-10 knockout (KO) mice on an NZB background. The NZB IL-10 KO mice develop peritoneal B-1 cells with approximately the same frequency as heterozygous and wild-type littermates. In contrast, the development of malignant B-1 cells in the peripheral blood and spleen, observed in wild-type NZB, rarely occurred in the NZB IL-10 KO. Phenotypic analysis of surface marker expression in splenic B cells indicated that, in contrast to the NZB with malignant B-1 splenic lymphoma, the surface marker expression of NZB IL-10 KO splenic B cells indicated that the majority of the B cells were typical B-2 cells. In the absence of IL-10, spontaneously activated B cells and antiapoptotic gene expression were reduced and lymphoma incidence was decreased. These results indicate that IL-10 is a critical factor for the progression of this B-cell malignant disease.