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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   29 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

Authors

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate 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
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5