H-2z homozygous New Zealand mice as a model for B-cell chronic lymphocytic leukemia: elevated bcl-2 expression in CD5 B cells at premalignant and malignant stages.
In New Zealand mice, the major histocompatibility complex (MHC) controls the development of both autoimmune disease and B cell chronic lymphocytic leukemia (B-CLL). While H-2d/H-2z heterozygosity acts as one major predisposing genetic element for autoimmune disease, H-2z/H-2z homozygosity acts as an element for B-CLL. In the H-2z/H-2z homozygotes, there was an age-dependent increase in frequencies of CD5 B cells in the blood and spleen, and such CD5 B cells showed oligoclonal to monoclonal expansion, giving rise to B-CLL. B-CLL cells from these mice had surface phenotypes typical of CD5 B lineage cells, and expressed high levels of proto-oncogene bcl-2. Elevated bcl-2 expression was also observed in premalignant B cells in the aged mice, thereby suggesting that apoptosis-resistant, long-surviving CD5 B cells with a self-renewal capacity form the basis of malignant transformation. This model not only provides clues for analyzing multiple steps of genetic alterations involved in the generation of B-CLL, but also sheds light on the correlation between B-CLL and autoimmune disease.
Okamoto
H
H
Department of Pathology, Juntendo University School of Medicine, Tokyo.
Nishimura
H
H
Shinozaki
A
A
Zhang
D
D
Hirose
S
S
Shirai
T
T
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D018956:CD5 Antigens; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics; D006720:Homozygote; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013154:Spleen / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D018956:CD5 Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2