SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders.

Haematologica 2014 Aug

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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. Copyright© Ferrata Storti Foundation.

Citation

Giorgia Simonetti, Maria Teresa Sabrina Bertilaccio, Tania Veliz Rodriguez, Benedetta Apollonio, Antonis Dagklis, Martina Rocchi, Anna Innocenzi, Stefano Casola, Thomas H Winkler, Lars Nitschke, Maurilio Ponzoni, Federico Caligaris-Cappio, Paolo Ghia. SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders. Haematologica. 2014 Aug;99(8):1356-64