Abstract
The transmembrane receptor Notch1 plays a crucial role in differentiation and apoptosis of hematopoietic cells. To investigate the influence of Notch1 on apoptosis and cell growth of mature murine B cells, we transduced the murine B-lymphoma line NYC 31.1 with a constitutively active, intracellular form of human Notch1 (Notch1-ICT). NYC cells represent mature activated B cells that can be induced to undergo apoptosis by crosslinking of the B-cell receptor (BCR). In contrast to investigations in immature chicken B-cell lines, transduced Notch1-ICT did not affect cell cycle progression, cell growth or surface IgM levels in NYC cells and resulted only in a slight induction of apoptosis. However, BCR-crosslinking enhanced apoptosis, but did not influence cell cycle progression in Notch1-ICT-positive NYC cells. These data imply a distinct function of Notch1 in mature murine B-cells as compared to immature chicken B cells and provide further evidence for Notch1's involvement in B-cell differentiation and development.
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Abbreviations
- BCR:
-
B-cell receptor
- CBF1:
-
core binding factor 1
- Ig:
-
immunoglobulin
- Notch1-ICT:
-
constitutively active, intracellular domain of human Notch1
- Notch1-IC:
-
constitutively active, intracellular domain of Notch1
- NP-40:
-
Nonidet P-40
- OPA:
-
glutamine-rich region
- PAGE:
-
polyacrylamide gel electrophoresis
- PEST:
-
proline (P), glutamine (E), serine (S) and threonine (T)-rich region
- PCR:
-
polymerase chain reaction
- RBP-J:
-
recombination signal binding protein Jkappa
- RT:
-
reverse transcription
- TAN:
-
translocation-associated human Notch1 homologue
- TCR:
-
T-cell receptor
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Acknowledgements
We thank Christine Matzner for excellent technical assistance and W Bielke (Erlangen) for advice, support and critical reading of the manuscript. The authors are grateful to Warren Pear for providing the retroviral vectors MSCV 2.1 and pGD-ICT. This work was supported in part by the research training grant GRK 592 from the German Research Society (DFG) to SR, the project grant SFB 263 from the DFG to US, BMJ and H-MJ, and intramural funding through the ELAN program of the University of Erlangen to H-MJ BMJ was supported by a fellowship from the German Cancer Research Center, Heidelberg (DKFZ), Germany.
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Romer, S., Saunders, U., Jäck, HM. et al. Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells without affecting cell cycle progression and surface IgM expression. Cell Death Differ 10, 833–844 (2003). https://doi.org/10.1038/sj.cdd.4401253
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DOI: https://doi.org/10.1038/sj.cdd.4401253
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