The low-affinity receptor for immunoglobulin G, FcγRIIB, is expressed on most B-cells and on immature and activated mature T-cells. Co-aggregation of FcγRIIB with the B-cell antigen receptor (BCR) leads to attenuation of BCR-induced blastogenesis and cell proliferation via inhibition of p21ras, phosphatidylinositol 3-kinase (PI3-K) and phospholipase Cγ (PLCγ) activation. These effects are mediated, at least in part, by the recruitment of SH2-containing protein tyrosine phosphatase-1 (SHP-1) and -2 (SHP-2) and SH2-containing inositol 5-phosphatase(SHIP). In this report, we demonstrate that FcγRIIB co-aggregation with the T-cell antigen receptor (TCR), which may occur when T-cells recognize antibody-coated target cells, leads to inhibition of TCR-induced phosphorylation of the linker of activated T-cells (LAT). When phosphorylated, LAT functions as an adapter molecule and recruits PI3-K. Additionally, we demonstrate that PI3-K is required for TCR-induced Ca2+ mobilization. Together, these data suggest that FcγRIIB may inhibit TCR-mediated Ca2+ mobilization, in part via inhibition of LAT phosphorylation and subsequent inhibition of PI3-K activation. A similar mechanism has been described in B-cells, where FcγRIIB co-aggregation with the BCR leads to inhibition of PI3-K activity via dephosphorylation of CD19. It is likely that, in both cell types, levels of PtdIns(3,4,5)P3 are additionally modulated via the enzymic activity of SHIP.
Skip Nav Destination
Article navigation
November 2001
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Conference Article|
November 01 2001
FcγRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization
V. L. Ott;
V. L. Ott
1Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, 1400 Jackson Street, Denver, CO 80206, U.S.A.
Search for other works by this author on:
J. C. Cambier
J. C. Cambier
3
1Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, 1400 Jackson Street, Denver, CO 80206, U.S.A.
3To whom correspondence should be addressed (e-mail cambierj@njc.org).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 08 2001
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2001 Biochemical Society
2001
Biochem Soc Trans (2001) 29 (6): 840–846.
Article history
Received:
June 08 2001
Citation
W. A. Jensen, S. Marschner, V. L. Ott, J. C. Cambier; FcγRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization. Biochem Soc Trans 1 November 2001; 29 (6): 840–846. doi: https://doi.org/10.1042/bst0290840
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.