Transgenic expression of helios in B lineage cells alters B cell properties and promotes lymphomagenesis

被引:26
作者
Dovat, S
Montecino-Rodriguez, E
Schuman, V
Teitell, MA
Dorshkind, K
Smale, ST
机构
[1] Univ Calif Los Angeles, Howard Hughes Med Inst, MacDonald Res Labs, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
[5] Mattel Childrens Hosp, Los Angeles, CA 90095 USA
关键词
D O I
10.4049/jimmunol.175.6.3508
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Helios, a member of the Maros 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.
引用
收藏
页码:3508 / 3515
页数:8
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