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 journalArticle

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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

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Lysosomes
Organelles
B-Lymphocytes
Apoptosis
Endosomes
Cathepsins
Cell Line
Cathepsin B
Enzyme Activation
B-Lymphoid Precursor Cells
Phosphatidylserines
Membrane Potentials
Chromatin
Enzymes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Lysosome is a primary organelle in B cell receptor-mediated apoptosis : An indispensable role of Syk in lysosomal function. / He, Jinsong; Tohyama, Yumi; Yamamoto, Ken-ichi; Kobayashi, Masahiko; Shi, Yuhong; Takano, Tomoko; Noda, Chiseko; Tohyama, Kaoru; Yamamura, Hirohei.

In: Genes to Cells, Vol. 10, No. 1, 01.2005, p. 23-35.

Research output: Contribution to journalArticle

He, Jinsong ; Tohyama, Yumi ; Yamamoto, Ken-ichi ; Kobayashi, Masahiko ; Shi, Yuhong ; Takano, Tomoko ; Noda, Chiseko ; Tohyama, Kaoru ; Yamamura, Hirohei. / Lysosome is a primary organelle in B cell receptor-mediated apoptosis : An indispensable role of Syk in lysosomal function. In: Genes to Cells. 2005 ; Vol. 10, No. 1. pp. 23-35.
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