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

Abstract

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.

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Correspondence to E Raveche.

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This work was supported by NIH R01 CA 71478-11 (ER) and a Graduate Student Fellowship from New Jersey Cancer Commission (BM)

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Czarneski, J., Lin, Y., Chong, S. et al. Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma. Leukemia 18, 597–606 (2004). https://doi.org/10.1038/sj.leu.2403244

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