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Abstract
Phospholipase C (PLC) plays important roles in phosphoinositide turnover by regulating the calcium-protein kinase C signaling pathway. PLC-L2 is a novel PLC-like protein which lacks PLC activity, although it is very homologous with PLC δ. PLC-L2 is expressed in hematopoietic cells, but its physiological roles and intracellular functions in the immune system have not yet been clarified. To elucidate the physiological function of PLC-L2, we generated mice which had a genetic PLC-L2 deficiency. PLC-L2-deficient mice grew with no apparent abnormalities. However, mature B cells from PLC-L2-deficient mice were hyperproliferative in response to B-cell receptor (BCR) cross-linking, although B2 cell development appeared to be normal. Molecular biological analysis revealed that calcium influx and NFATc accumulation in nuclei were increased in PLC-L2-deficient B cells. Extracellular signal-regulated kinase activity was also enhanced in PLC-L2-deficient B cells. These mice had a stronger T-cell-independent antigen response. These results indicate that PLC-L2 is a novel negative regulator of BCR signaling and immune responses.
ACKNOWLEDGMENTS
We thank S. Takaki and T. Tamura for helpful discussions and K. Miyake (The University of Tokyo) and T. Kurosaki (Kansai Medical University) for reading the manuscript. We also thank K. Horikawa, A. Kariyone, and F. Ma for technical advice, T. Nakamichi for technical assistance, and S. Nakae for materials (The University of Tokyo).
This work was supported by the Core Research for Evolution Science and Technology (CREST) division of the Japan Science and Technology Corporation.