First Author | Czarneski J | Year | 2004 |
Journal | Leukemia | Volume | 18 |
Issue | 3 | Pages | 597-606 |
PubMed ID | 14712288 | Mgi Jnum | J:88136 |
Mgi Id | MGI:3029161 | Doi | 10.1038/sj.leu.2403244 |
Citation | Czarneski J, et al. (2004) Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma. Leukemia 18(3):597-606 |
abstractText | 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. |