APOPTOSIS INDUCTION IN CD5(-CELLS()[LY1(+)] MALIGNANT B)

Apoptosis, or programmed cell death, was studied in B-1 (CD5+B) cells from NZB mice and their hybrids. NZB mice, as they age, develop clones of B-1 cells with the majority of the clones possessing extra chromos omes (hyperdiploid). These clones differ in growth characteristics, va rying from a slow-growing non-invasive clonal expansion of B-1 cells, similar to chronic lymphocytic leukemias (CLL), to an aggressive fast- growing invasive malignancy, similar to Richter's syndrome. Apoptosis was induced in cultures of B-1 cells purified from peritoneal wash-out cells with either anti-immunoglobulin (anti-IgM) or lipopolysaccharid e (LPS). The malignant hyperdiploid B-1 cells had increased apoptosis in response to these stimuli as determined by the presence of fragment ed DNA. The amount of apoptosis was directly related to the aggressive nature of the B-1 cells. The increased apoptosis observed in malignan t B-1 cells was also correlated with the state of activation of the ce lls. Malignant B-1 cells undergoing high levels of apoptosis had high spontaneous activation and IgM production. The supernatant levels of I gM in unstimulated cultures of aggressive malignant B-1 cells were the same as that stimulated with LPS, indicating that the malignant B-1 c lones were maximally activated in vivo. In conclusion, hyperdiploid B- 1 cells appear to have altered responses to stimuli that normally acti vate mature B cells. A signal for apoptosis rather than stimulation ma y result when malignant B-1 clones have their antigen receptors engage d. The increased apoptosis capability of malignant B-1 cells may be ex ploited as a therapeutic tool.