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Publication : Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis.

First Author  Dovat S Year  2005
Journal  J Immunol Volume  175
Issue  6 Pages  3508-15
PubMed ID  16148093 Mgi Jnum  J:103729
Mgi Id  MGI:3610660 Doi  10.4049/jimmunol.175.6.3508
Citation  Dovat S, et al. (2005) Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis. J Immunol 175(6):3508-15
abstractText  Helios, a member of the Ikaros family of DNA-binding proteins, is expressed in multipotential lymphoid progenitors and throughout the T lineage. However, in most B lineage cells, Helios is not expressed, suggesting that its absence may be critical for B cell development and function. To test this possibility, transgenic mice were generated that express Helios under the control of an Ig mu enhancer. Commitment to the B cell lineage was unaltered in Helios transgenic mice, and numbers of surface IgM(+) B cells were normal in the bone marrow and spleen. However, both bone marrow and splenic B cells exhibited prolonged survival and enhanced proliferation. B cells in Helios transgenic mice were also hyperresponsive to Ag stimulation. These alterations were observed even though the concentration of ectopic Helios in B lineage cells, like that of endogenous Helios in thymocytes, was well below the concentration of Ikaros. Further evidence that ectopic Helios expression contributes to B cell abnormalities was provided by the observation that Helios transgenic mice developed metastatic lymphoma as they aged. Taken together, these results demonstrate that silencing of Helios is critical for normal B cell function.
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