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

Leukemia. 2004 Mar;18(3):597-606. doi: 10.1038/sj.leu.2403244.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / pathology
  • Crosses, Genetic
  • Disease Progression
  • Female
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Lymphocyte Activation
  • Lymphoma, B-Cell / etiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Mice, Knockout
  • Mice, Transgenic
  • RNA, Messenger / analysis
  • Spleen / pathology
  • Splenic Neoplasms / etiology

Substances

  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • Interleukin-10