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An important role of phospholipase Cgamma1 in pre-B-cell development and allelic exclusion. EMBO J 2004 Oct 13;23(20):4007-17

Date

09/17/2004

Pubmed ID

15372077

Pubmed Central ID

PMC524341

DOI

10.1038/sj.emboj.7600405

Scopus ID

2-s2.0-8144221736 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

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.

Author List

Wen R, Chen Y, Schuman J, Fu G, Yang S, Zhang W, Newman DK, Wang D

Author

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alleles
Animals
B-Lymphocytes
Crosses, Genetic
Hematopoietic Stem Cells
Mice
Mice, Knockout
Mice, Transgenic
Phospholipase C gamma
Type C Phospholipases