Apoptosis induced in Burkitt's lymphoma cells via Gb3/CD77, a glycolipid antigen.
Gb3/CD77 is a glycolipid antigen, specifically expressed on two different B-cell populations, Burkitt's lymphoma and a subset of tonsillar B-lymphocytes located in germinal centers, which could be the normal counterpart of Burkitt cells. Both Gb3/CD77(+) populations have recently been shown to enter programmed cell death (apoptosis) readily. Here we show that verotoxin, also called Shiga-like toxin, which is known to bind to the carbohydrate moiety of Gb3/CD77, induces cell death in Gb3/CD77(+) Burkitt's lymphoma cells, not only by inhibiting protein synthesis as classically described but also through an additional mechanism, namely apoptosis. Furthermore a recombinant B-subunit of verotoxin, which carries only the binding property of the holotoxin, also induces apoptosis in Gb3/CD77(+) cells. Gb3/CD77 could thus represent the first example of a glycolipid antigen able to transduce a signal leading to apoptosis.
Mangeney
M
M
Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Villejuif, France.
Lingwood
C A
CA
Taga
S
S
Caillou
B
B
Tursz
T
T
Wiels
J
J
D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D002051:Burkitt Lymphoma / Q000473:pathology* / Q000648:ultrastructure; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008970:Molecular Weight; D011994:Recombinant Proteins / Q000633:toxicity; D015183:Restriction Mapping; D022622:Shiga Toxin 1; D014281:Trihexosylceramides / Q000096:biosynthesis / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D001427:Bacterial Toxins; D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D022622:Shiga Toxin 1; D014281:Trihexosylceramides; C018549:globotriaosylceramide