Faculty Collaboration Database

Distinct roles of phosphoinositide-3 kinase and phospholipase Cgamma2 in B-cell receptor-mediated signal transduction. Mol Cell Biol 2006 Jan;26(1):88-99

Date

12/16/2005

Pubmed ID

16354682

Pubmed Central ID

PMC1317611

DOI

10.1128/MCB.26.1.88-99.2006

Scopus ID

2-s2.0-33645237961 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

During B-cell receptor (BCR) signaling, phosphoinositide-3 kinase (PI3K) is thought to function upstream of phospholipase Cgamma2 (PLCgamma2). PLCgamma2 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 PLCgamma2 using PI3K-/-, PLCgamma2-/-, and PI3K-/- PLCgamma2-/- B cells. Interestingly, PLCgamma2 deficiency had no effect on BCR-mediated PI3K activation, whereas PI3K deficiency only partially blocked activation of PLCgamma2. Moreover, whereas PI3K-/- PLCgamma2-/- double deficiency did not affect hematopoiesis, it resulted in embryonic lethality. PI3K-/- PLCgamma2-/- 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 PLCgamma2 single-deficiency B cells. Consistent with this finding, BCR signaling was more severely impaired in the absence of both PI3K and PLCgamma2 genes than in the absence of either one alone. Taken together, these results demonstrate that whereas PI3K functions upstream of PLCgamma2, activation of PLCgamma2 can occur independently of PI3K and that PI3K and PLCgamma2 also have distinct functions in BCR signal transduction.

Author List

Dai X, Chen Y, Schuman J, Hua Z, Adamson JW, Wen R, Wang D

Authors

Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin

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

Animals
B-Lymphocytes
Cell Differentiation
Embryo, Mammalian
Embryonic Development
Enzyme Activation
Gene Deletion
Lymphocyte Activation
Mice
Mice, Mutant Strains
Phosphatidylinositol 3-Kinases
Phospholipase C gamma
Receptors, Antigen, B-Cell
Signal Transduction