H-2^z Homozygous New Zealand mice as a model for B-cell chronic lymphocytic leukemia

elevated bcl-2 expression in CD5 B-cells at premalignant and at malignant stages.

Abstract

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-2^d/H-2^z heterozygosity acts as one major predisposing genetic element for autoimmune disease, H-2^z/H-2^z homozygosity acts as an elenent for B-CLL. In the H-2^z/H-2^z homozygotes, there was an age-dependent increase in the percentage of CD5 B cells in the blood and spleen, and such CD5 B cells were oligoclonal to monoclonal expansion, giving rise to B-CLL. B-CLL cell from these mice had surface phenotypes typical of the CD5 B lineage cells, and expressed ligh levels of proto-oncogene bcl-2 expression was also observed in the 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 is useful for analyzing multiple steps of genetic alterations involved in the generation of B-CLL, and for clarifying the relationship between B-CLL and autoimmune disease.