Mouse mast cell gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when coligated with the high-affinity Fc receptor for IgE.
Open accessAbstract
Mouse mast cells express gp49B1, a cell-surface member of the Ig superfamily encoded by the gp49B gene. We now report that by ALIGN comparison of the amino acid sequence of gp49B1 with numerous receptors of the Ig superfamily, a newly recognized family has been established that includes gp49B1, the human myeloid cell Fc receptor for IgA, the bovine myeloid cell Fc receptor for IgG2, and the human killer cell inhibitory receptors expressed on natural killer cells and T lymphocyte subsets. Furthermore, the cytoplasmic domain of gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs that are also present in killer cell inhibitory receptors; these motifs downregulate natural killer cell and T-cell activation signals that lead to cytotoxic activity. As assessed by flow cytometry with transfectants that express either gp49B1 or gp49A, which are 89% identical in the amino acid sequences of their extracellular domains, mAb B23.1 was shown to recognize only gp49B1. Coligation of mAb B23.1 bound to gp49B1 and IgE fixed to the high-affinity Fc receptor for IgE on the surface of mouse bone marrow-derived mast cells inhibited exocytosis in a dose-related manner, as defined by the release of the secretory granule constituent beta-hexosaminidase, as well as the generation of the membrane-derived lipid mediator, leukotriene C4. Thus, gp49B1 is an immunoreceptor tyrosine-based inhibition motif-containing integral cell-surface protein that downregulates the high-affinity Fc receptor for IgE-mediated release of proinflammatory mediators from mast cells. Our findings establish a novel counterregulatory transmembrane pathway by which mast cell activation can be inhibited.
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LILRBs are expressed predominantly on myeloid cells and their murine relatives PirB and gp49B1 differ in expression patterns and ligand specificity.
“LILRBs are expressed predominantly on myeloid cells and their murine relatives—PirB and gp49B121,22—differ in both expression patterns and ligand specificity.”
From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [22]
The opening passage (section and page not supplied) identifies gp49B1 as a mouse mast-cell receptor in a family that includes human myeloid receptors, supporting its identification as a murine relative. It does not discuss PirB or compare PirB and gp49B1 expression patterns or ligand specificity. (LLM, conf=0.84)
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- Authors
- Katz, H. R., Vivier, E., Castells, M. C., McCormick, M. J., Chambers, J. M., & Austen, K. F.
- Affiliations
- Harvard University (US)
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. hkatz@warren.med.harvard.edu
- Centre National de la Recherche Scientifique (FR)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-10
- Volume
- 93
- Issue
- 20
- Pages
- 10809-10814
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC38237
- OpenAlex
- W1969075833
- Cited by
- 155
- References
- 0
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- National Institute of Allergy and Infectious Diseases (AI 07306, AI 22531, AI-21101, T32AI007306)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- mast cells, immunoreceptor tyrosine-based inhibition motif, mast cell activation, exocytosis, beta-hexosaminidase, leukotriene C4, killer cell inhibitory receptors, natural killer cells, T cells, transmembrane proteins
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antigens, Surface, beta-N-Acetylhexosaminidases, Cells, Cultured, Male, Mast Cells, Membrane Glycoproteins, Mice, Inbred BALB C, Molecular Sequence Data, Peptides, Receptor Aggregation, Receptors, Immunologic, Tyrosine, Signal Transduction, Consensus Sequence, Sequence Alignment, Sequence Homology, Amino Acid, Receptors, IgE, Mice
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