Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B.
The potential of the paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) types for modifying an IgE antibody-mediated allergic response was evaluated in mouse bone marrow-derived mast cells. Although mast cells produced both PIR-A and PIR-B, PIR-B was found to be preferentially expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with intracellular SHP-1 protein tyrosine phosphatase. PIR-B coligation with the IgE receptor (FcepsilonRI) inhibited IgE-mediated mast cell activation and release of serotonin. Surprisingly, the inhibitory activity of PIR-B was unimpaired in SHP-1-deficient mast cells. A third functional tyrosine-based inhibitory motif, one that fails to bind the SHP-1, SHP-2, and SHIP phosphatases, was identified in parallel studies of FcepsilonRI-bearing rat basophilic leukemia (RBL) cells transfected with constructs having mutations in the PIR-B cytoplasmic region. These results define the preferential expression of the PIR-B molecules on mast cells and an inhibitory potential that can be mediated via a SHP-1-independent pathway.
Uehara
T
T
Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.
Bléry
M
M
Kang
D W
DW
Chen
C C
CC
Ho
L H
LH
Gartland
G L
GL
Liu
F T
FT
Vivier
E
E
Cooper
M D
MD
Kubagawa
H
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D017455:Receptors, IgE / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D012701:Serotonin / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism
C105949:Pirb protein, mouse; C491380:Pirb protein, rat; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D012701:Serotonin; D007073:Immunoglobulin E; D014443:Tyrosine; D002118:Calcium