title: Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor PIR-B.
abstract: 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.
authors.affiliation: Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300, USA.
authors.forename: T
authors.initials: T
authors.lastname: Uehara
authors.forename: M
authors.initials: M
authors.lastname: Bléry
authors.forename: D W
authors.initials: DW
authors.lastname: Kang
authors.forename: C C
authors.initials: CC
authors.lastname: Chen
authors.forename: L H
authors.initials: LH
authors.lastname: Ho
authors.forename: G L
authors.initials: GL
authors.lastname: Gartland
authors.forename: F T
authors.initials: FT
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Vivier
authors.forename: M D
authors.initials: MD
authors.lastname: Cooper
authors.forename: H
authors.initials: H
authors.lastname: Kubagawa
mesh_terms: 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
chemical_list: C105949:Pirb protein, mouse; C491380:Pirb protein, rat; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D012701:Serotonin; D007073:Immunoglobulin E; D014443:Tyrosine; D002118:Calcium