Transgenic expression of Helios in B lineage cells alters B cell properties and promotes lymphomagenesis.
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.
Dovat
Sinisa
S
Mattel Children's Hospital and Department of Pediatrics, University of California, Los Angeles, CA 90095, USA.
Montecino-Rodriguez
Encarnacion
E
Schuman
Valerie
V
Teitell
Michael A
MA
Dorshkind
Kenneth
K
Smale
Stephen T
ST
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells; D019070:Cell Lineage; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005822:Genetic Vectors; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D013154:Spleen / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse