Lysosome is a primary organelle in B cell receptor-mediated apoptosis: an indispensable role of Syk in lysosomal function

被引:32
作者
He, J
Tohyama, Y
Yamamoto, K
Kobayashi, M
Shi, Y
Takano, T
Noda, C
Tohyama, K
Yamamura, H [1 ]
机构
[1] Kobe Univ, Grad Sch Med, Dept Genome Sci, Kobe, Hyogo 6500017, Japan
[2] Kanazawa Univ, Canc Res Inst, Dept Mol Pathol, Kanazawa, Ishikawa 9200934, Japan
[3] Hyogo Univ, Dept Nutr Management, Kakogawa 6750101, Japan
[4] Kawasaki Med Sch, Dept Lab Med & Clin Pathol, Kurashiki, Okayama 7010192, Japan
关键词
D O I
10.1111/j.1365-2443.2004.00811.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To investigate the mechanism of B cell receptor (BCR)-mediated apoptosis, we utilized immature B cell lines, DT40 and WEHI-231. In both cell lines, BCR-crosslinking caused the increase in lysosomal pH with early apoptotic changes characterized by chromatin condensation and phosphatidylserine exposure. This increase was detected in c-Abl-deficient DT40 cells but not in Syk-deficient cells, which corresponded to the fact that the former cells but not the latter revealed BCR-induced apoptosis. In contrast, BCR-crosslinking caused no apparent change in mitochondrial transmembrane potential. Therefore, the lysosomal change might be a primary event in BCR-induced apoptosis in DT40 cells. The increased activity of cathepsin B and apoptosis-preventing effect of a cathepsin inhibitor suggested a significant role of lysosomal enzymes in this apoptosis. By microscopic studies, lysosomes of wild-type DT40 cells fused to BCR-carrying endosomes became enlarged and accumulated one another. In contrast, these changes of lysosomal dynamics did not occur in Syk-deficient cells but transfer of wild-type Syk restored the lysosomal changes and apoptosis. These results demonstrated that the lysosomal change accompanied with the activation of lysosomal enzymes is a primary step in BCR-crosslinking-mediated apoptosis and Syk is responsible for this step through the fusion of BCR-carrying endosomes to lysosomes.
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页码:23 / 35
页数:13
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