Comparative susceptibility of B cells with different lineages to cytotoxicity and apoptosis induction by translational inhibitors.
The trichothecene mycotoxins, Shiga toxins (STs), and ricin are potent translational inhibitors that exert diverse mechanisms of action but all have the capacity to induce death by apoptosis. Germinal centers containing actively dividing B cells are particularly sensitive to protein synthesis inhibition, and, of these, the immature B cell is reportedly most susceptible to apoptosis. The objective of this study was to test the hypothesis that immature and mature B-cell lineages were differentially susceptible to apoptosis and cytotoxicity induction by representative trichothecene mycotoxins, ST-1, and ricin, as well as cycloheximide (CHX), a prototypical protein synthesis inhibitor commonly used to study cell signal transduction. WEHI-231 and CH31 cells were used as representatives of phenotypically immature B cells, whereas CH12.LX cells were used to model mature B cells. Resultant data suggest that Type D and Type A trichothecenes, ricin, and ST-1 were more potent inducers of apoptosis than CHX, whereas Type B and Type A trichothecene metabolites were less. CHX and the trichothecenes affected immature and mature B cells equally, thus suggesting that toxicity due to these natural toxins was lineage independent. In contrast, mature B cells were more sensitive to ricin- and ST-1-induced cytotoxicity and apoptosis than immature B cells. Taken together, these results suggest that B cells are targets of a diverse array of naturally occurring translational inhibitors. Upregulation of apoptosis in B lymphocytes may contribute to the impairment of the immune response and other symptoms described following exposure to these toxins.
Uzarski
Rebecca L
RL
Department of Food Science and Human Nutrition, Institute for Environmental Toxicology, Michigan State University, East Lansing, MI 48824-1224, USA.
Pestka
James J
JJ
D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D018929:Cell Culture Techniques; D016923:Cell Death; D002454:Cell Differentiation; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects; D012276:Ricin / Q000633:toxicity*; D022603:Shiga Toxins / Q000633:toxicity*; D014255:Trichothecenes / Q000633:toxicity*; D015854:Up-Regulation
D022603:Shiga Toxins; D014255:Trichothecenes; D012276:Ricin