This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dai, X. Articles by Wang, D. Search for Related Content PubMed PubMed Citation Articles by Dai, X. Articles by Wang, D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2006, p. 88-99, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.88-99.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Distinct Roles of Phosphoinositide-3 Kinase and Phospholipase C2 in B-Cell Receptor-Mediated Signal Transduction

Blood Research Institute, Blood Center of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, Wisconsin 53226,¹ State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China,² Department of Medicine,³ Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, Wisconsin 53226⁴

Received 23 April 2005/ Returned for modification 7 July 2005/ Accepted 8 October 2005

During B-cell receptor (BCR) signaling, phosphoinositide-3 kinase (PI3K) is thought to function upstream of phospholipase C2 (PLC2). PLC2 deficiency specifically impedes transitional type 2 (T2) to follicular (FO) mature B-cell transition. Here, we demonstrate that PI3K deficiency specifically impaired T2-to-FO mature B-cell transition and marginal zone B-cell development. Furthermore, we investigated the functional relationship between PI3K and PLC2 using PI3K^–/–, PLC2^–/–, and PI3K^–/– PLC2^–/– B cells. Interestingly, PLC2 deficiency had no effect on BCR-mediated PI3K activation, whereas PI3K deficiency only partially blocked activation of PLC2. Moreover, whereas PI3K^–/– PLC2^–/– double deficiency did not affect hematopoiesis, it resulted in embryonic lethality. PI3K^–/– PLC2^–/– fetal liver cells transplanted into B-cell null JAK3^–/– mice failed to restore development of peripheral B cells and failed to progress through early B-cell development at the pro-B- to pre-B-cell transition, a more severe phenotype than was observed with either PI3K or PLC2 single-deficiency B cells. Consistent with this finding, BCR signaling was more severely impaired in the absence of both PI3K and PLC2 genes than in the absence of either one alone. Taken together, these results demonstrate that whereas PI3K functions upstream of PLC2, activation of PLC2 can occur independently of PI3K and that PI3K and PLC2 also have distinct functions in BCR signal transduction.

This article has been cited by other articles:

• Cariappa, A., Boboila, C., Moran, S. T., Liu, H., Shi, H. N., Pillai, S. (2007). The Recirculating B Cell Pool Contains Two Functionally Distinct, Long-Lived, Posttransitional, Follicular B Cell Populations. J. Immunol. 179: 2270-2281 [Abstract] [Full Text]  
• Hoek, K. L., Antony, P., Lowe, J., Shinners, N., Sarmah, B., Wente, S. R., Wang, D., Gerstein, R. M., Khan, W. N. (2006). Transitional B Cell Fate Is Associated with Developmental Stage-Specific Regulation of Diacylglycerol and Calcium Signaling upon B Cell Receptor Engagement. J. Immunol. 177: 5405-5413 [Abstract] [Full Text]