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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3377-3384. Prepublished online as a Blood First Edition Paper on December 12, 2006; DOI 10.1182/blood-2006-07-036418. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-036418v1 109/8/3377    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Xu, S. Articles by Lam, K.-P. Search for Related Content PubMed PubMed Citation Articles by Xu, S. Articles by Lam, K.-P. Related Collections Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Combined deficiencies in Bruton tyrosine kinase and phospholipase C2 arrest B-cell development at a pre-BCR+ stage Shengli Xu1, Koon-Guan Lee1, Jianxin Huo1, Tomohiro Kurosaki2, and Kong-Peng Lam1 1 Laboratory of Molecular and Cellular Immunology, Biomedical Sciences Institute, Agency for Science, Technology and Research (A*STAR) and Singapore Immunology Network (SIgN), Singapore; 2 Laboratory of Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan Bruton tyrosine kinase (Btk) and phospholipase C2 (PLC2) are 2 key molecules involved in B-cell receptor (BCR) signaling. Biochemical studies have placed them in a linear signaling pathway, with Btk acting upstream of PLC2. Consistent with this, mice lacking either molecule display a leaky but similar block in B-cell development. Here, we generated Btk–/– PLC2–/– mice and showed that combined deficiencies in Btk and PLC2 severely arrested B lymphopoiesis at the large pre–B-cell stage. In contrast to either single mutant, Btk–/– PLC2–/– pre–B cells expressed high levels of pre-BCR on their cell surfaces and exhibited reduced immunoglobulin light chain gene rearrangements. Pre-BCR–induced calcium signaling was also drastically compromised in Btk–/– PLC2–/– pre–B cells compared with wild-type and single-mutant cells. Interestingly, immunoglobulin heavy chain allelic exclusion remained intact in the absence of Btk and PLC2. Overall, our results suggest that Btk and PLC2 have combinatorial roles in regulating pre–B cell differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Xu, J. Huo, K.-G. Lee, T. Kurosaki, and K.-P. Lam Phospholipase C{gamma}2 Is Critical for Dectin-1-mediated Ca2+ Flux and Cytokine Production in Dendritic Cells J. Biol. Chem., March 13, 2009; 284(11): 7038 - 7046. [Abstract] [Full Text] [PDF] J. Nakayama, M. Yamamoto, K. Hayashi, H. Satoh, K. Bundo, M. Kubo, R. Goitsuka, M. A. Farrar, and D. Kitamura BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3 Blood, February 12, 2009; 113(7): 1483 - 1492. [Abstract] [Full Text] [PDF] A. Oda, T. Ono, M. Yamamoto, R. Goitsuka, and D. Kitamura PKC{eta} directs induction of IRF-4 expression and Ig {kappa} gene rearrangement in pre-BCR signaling pathway Int. Immunol., November 1, 2008; 20(11): 1417 - 1426. [Abstract] [Full Text] [PDF] S. Ma, S. Pathak, L. Trinh, and R. Lu Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre-B-cell receptor and promote cell-cycle withdrawal in pre-B-cell development Blood, February 1, 2008; 111(3): 1396 - 1403. [Abstract] [Full Text] [PDF]

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