In vivo expansion of the endogenous B-cell compartment stimulated by radiation and serial bone marrow transplantation induces B-cell leukaemia in mice

Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells. This B-cell lineage is established during ontogeny and replenished by the proce ss of self-renewal. Spontaneous and induced leukaemias that frequently affe ct this lineage are thought to arise as a result of the frequent cell divis ion required to maintain the population throughout adulthood and in respons e to repeated exposure to environmental antigens. In a series of bone marro w transplant (BMT) experiments performed in B6D2F1 mice, B-cell leukaemia o ccurred in recipients of serially transplanted syngeneic bone marrow. This study was therefore designed to determine the frequency and phenotype of th e observed leukaemia. Male donor cells were initially transplanted into let hally irradiated female hosts and secondary (2 degrees) BMT was performed a t 3 months. At 1, 2, 3 and 16 months following primary (1 degrees) BMT, and when 2 degrees BMT recipients developed leukaemia, animals were sacrificed and their tissues extensively examined. These analyses confirmed a host-de rived CD5(+) transplantable B-cell leukaemia that was initiated in 50% of 1 degrees BMT recipients. With serial passage, the leukaemia became more agg ressive and lost CD5 expression, suggesting transformation to a high-grade leukaemia/lymphoma. This previously unreported observation suggests that th e combination of radiation and subsequent serial transplantation induces a proliferative stress to the host B-cell compartment that is causative in le ukaemic transformation.