Apoptosis induction in CD5+(Ly1+) malignant B cells.
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 chromosomes (hyperdiploid). These clones differ in growth characteristics, varying 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 lipopolysaccharide (LPS). The malignant hyperdiploid B-1 cells had increased apoptosis in response to these stimuli as determined by the presence of fragmented DNA. The amount of apoptosis was directly related to the aggressive nature of the B-1 cells. The increased apoptosis observed in malignant B-1 cells was also correlated with the state of activation of the cells. Malignant B-1 cells undergoing high levels of apoptosis had high spontaneous activation and IgM production. The supernatant levels of IgM in unstimulated cultures of aggressive malignant B-1 cells were the same as that stimulated with LPS, indicating that the malignant B-1 clones were maximally activated in vivo. In conclusion, hyperdiploid B-1 cells appear to have altered responses to stimuli that normally activate mature B cells. A signal for apoptosis rather than stimulation may result when malignant B-1 clones have their antigen receptors engaged. The increased apoptosis capability of malignant B-1 cells may be exploited as a therapeutic tool.
Peng
B
B
Department of Pathology, UMDNJ/New Jersey Medical School, Newark 07103.
Raveche
E
E
D000367:Age Factors; D000782:Aneuploidy; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000648:ultrastructure; D018956:CD5 Antigens; D002999:Clone Cells; D004249:DNA Damage; D005260:Female; D007075:Immunoglobulin M / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009374:Neoplasms, Experimental / Q000473:pathology
D015703:Antigens, CD; D018956:CD5 Antigens; D007075:Immunoglobulin M; D008070:Lipopolysaccharides