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  • The EMBO Journal (2004) 23, 4007 - 4017
  • doi:10.1038/sj.emboj.7600405

Published online: 16 September 2004

An important role of phospholipase Cbig gamma1 in pre-B-cell development and allelic exclusion

Renren Wen1, Yuhong Chen1,2, James Schuman1, Guoping Fu1, Shoua Yang1, Weiguo Zhang3, Debra K Newman1,4 and Demin Wang1,2,4

  1. The Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA
  2. Model Research Animal Center, The Institute of Molecular Medicine, Nanjing University, Nanjing, PR China
  3. Department of Immunology, Duke University Medical Center, Durham, NC, USA
  4. Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA

Correspondence to:

Demin Wang, The Blood Research Institute, The Blood Center of Southeastern Wisconsin, 8727, Watertown Plank Road, Milwaukee, WI 53226, USA. Tel.: +1 414 937 3874; Fax: +1 414 937 3838; E-mail: dwang@bcsew.edu

Received 12 January 2004; Accepted 16 August 2004

Phospholipase Cgamma1 (PLCgamma1) has been reported to be expressed predominantly in T cells and to play an important role in T-cell receptor signaling. Here we show that PLCgamma1 is expressed throughout B-cell development, with high expression in B-cell progenitors, and is involved in pre-B-cell receptor (pre-BCR) signaling. Reduced expression of PLCgamma1, in the absence of PLCgamma2 (PLCgamma1+/-PLCgamma2-/-), impedes early B-cell development at the pro-B- to pre-B-cell transition and impairs immunoglobulin heavy chain allelic exclusion, hallmarks of defective pre-BCR signaling. In contrast, early B-cell development is largely normal, whereas late B-cell maturation is impaired in the absence of PLCgamma2 alone (PLCgamma2-/-) and overexpression of PLCgamma1 in PLCgamma2-/- mice fails to restore BCR-mediated B-cell proliferation and maturation. These studies reveal an essential role of PLCgamma1, distinct from that of PLCgamma2, in B-cell development.

  • Keywords:

    • allelic exclusion,
    • B-cell development,
    • phospholipase Cgamma1,
    • pre-B-cell receptor