Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma

被引:45
作者
Czarneski, J
Lin, YC
Chong, S
McCarthy, B
Fernandes, H
Parker, G
Mansour, A
Huppi, K
Marti, GE
Raveche, E
机构
[1] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol, Newark, NJ 07103 USA
[2] NCI, Canc Prevent Studies Branch, NIH, Rockville, MD USA
[3] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA
关键词
B-lymphocytes; cytokines; knockout;
D O I
10.1038/sj.leu.2403244
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:597 / 606
页数:10
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