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SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders
- Source :
- Haematologica, Vol 99, Iss 8 (2014)
- Publication Year :
- 2014
- Publisher :
- Ferrata Storti Foundation, 2014.
-
Abstract
- The sialic-acid-binding immunoglobulin-like lectin SIGLEC-G is a negative regulator of B-cell receptor-mediated calcium signaling. Its deficiency leads to reduced turnover and increased proliferation and survival of murine B-1a cells. Siglecg−/− mice show a premature expansion of polyclonal CD5+ B cells in the spleen and the peritoneal cavity. Here we studied the fate of B lymphocytes in Siglecg−/− mice over time. We demonstrate that in aging animals SIGLEC-G deficiency promotes progressive accumulation of monoclonal B lymphocytes and increases the susceptibility to develop B-cell lymphoproliferative disorders. Lymphoid tumors arising in aged Siglecg−/− mice are monoclonal and histologically heterogeneous as they include diffuse large B-cell lymphoma, follicular lymphoma, and medium-to-large B-cell monomorphic lymphoma but surprisingly not chronic lymphocytic leukemia. The tumors express high levels of BCL-2 and are transplantable. In keeping with these findings we have also observed a remarkable down-regulation of the human ortholog SIGLEC10 in human B-cell lymphoma and leukemia cell lines. Taken together, these observations indicate that the down-regulation of negative B-cell receptor regulators such as SIGLEC-G/SIGLEC10 may represent another mechanism relevant to the pathogenesis of B-cell lymphomas.
- Subjects :
- Diseases of the blood and blood-forming organs
RC633-647.5
Subjects
Details
- Language :
- English
- ISSN :
- 03906078 and 15928721
- Volume :
- 99
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7ce3840a3ef74bce947ab87c5f066183
- Document Type :
- article
- Full Text :
- https://doi.org/10.3324/haematol.2013.100230