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

Jinsong He, Yumi Tohyama, Ken Ichi Yamamoto, Masahiko Kobayashi, Yuhong Shi, Tomoko Takano, Chiseko Noda, Kaoru Tohyama, Hirohei Yamamura

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)23-35
Number of pages13
JournalGenes to Cells
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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