Mice lacking the ITIM-containing receptor G6b-B exhibit macrothrombocytopenia and aberrant platelet function
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Updated: May 17, 2026
Purification of Platelets from Mouse Blood
Published on: May 7, 2019
Alexandra Mazharian1, Ying-Jie Wang1, Jun Mori1
1Centre of Cardiovascular Sciences, Institute of Biomedical Research, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Abstract:
Platelets are highly reactive cell fragments that adhere to exposed extracellular matrix (ECM) and prevent excessive blood loss by forming clots. Paradoxically, megakaryocytes, which produce platelets in the bone marrow, remain relatively refractory to the ECM-rich environment of the bone marrow despite having the same repertoire of receptors as platelets. These include the ITAM (immunoreceptor tyrosine-based activation motif)-containing collagen receptor complex, which consists of glycoprotein VI (GPVI) and the Fc receptor γ-chain, and the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing receptor G6b-B. We showed that mice lacking G6b-B exhibited macrothrombocytopenia (reduced platelet numbers and the presence of enlarged platelets) and a susceptibility to bleeding as a result of aberrant platelet production and function. Platelet numbers were markedly reduced in G6b-B-deficient mice compared to those in wild-type mice because of increased platelet turnover. Furthermore, megakaryocytes in G6b-B-deficient mice showed enhanced metalloproteinase production, which led to increased shedding of cell-surface receptors, including GPVI and GPIbα. In addition, G6b-B-deficient megakaryocytes exhibited reduced integrin-mediated functions and defective formation of proplatelets, the long filamentous projections from which platelets bud off. Together, these findings establish G6b-B as a major inhibitory receptor regulating megakaryocyte activation, function, and platelet production.
Insights
The inhibitory receptor G6b-B is crucial for regulating megakaryocyte function and platelet production. Its absence leads to macrothrombocytopenia and bleeding due to impaired platelet formation.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Platelets are essential for hemostasis, preventing blood loss via clot formation.
- Megakaryocytes, platelet-producing cells, are paradoxically less responsive to the bone marrow's extracellular matrix (ECM) than platelets.
- Key receptors like GPVI and G6b-B are present on both cell types.
Purpose of the Study:
- To investigate the role of the ITIM-containing receptor G6b-B in megakaryocyte function and platelet production.
- To understand the consequences of G6b-B deficiency on platelet counts and bleeding susceptibility.
Main Methods:
- Utilized G6b-B-deficient mice models.
- Analyzed platelet numbers, size, and turnover.
- Assessed megakaryocyte metalloproteinase production, receptor shedding, integrin function, and proplatelet formation.
Main Results:
- G6b-B deficient mice exhibited macrothrombocytopenia (low platelet count, enlarged platelets) and increased bleeding.
- Platelet numbers were reduced due to increased turnover.
- Megakaryocytes in deficient mice showed enhanced metalloproteinase activity, leading to receptor shedding (GPVI, GPIbα), impaired integrin function, and defective proplatelet formation.
Conclusions:
- G6b-B acts as a critical inhibitory receptor in megakaryocytes.
- G6b-B regulates megakaryocyte activation, receptor shedding, and proplatelet formation.
- Deficiency in G6b-B disrupts platelet production and contributes to bleeding disorders.
