Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma.
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.
Czarneski
J
J
Department of Pathology, New Jersey Medical School, Newark, NJ, USA.
Lin
Y C
YC
Chong
S
S
McCarthy
B
B
Fernandes
H
H
Parker
G
G
Mansour
A
A
Huppi
K
K
Marti
G E
GE
Raveche
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D003433:Crosses, Genetic; D018450:Disease Progression; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000473:pathology; D013160:Splenic Neoplasms / Q000209:etiology
D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10