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

Sinisa Dovat, Encarnacion Montecino-Rodriguez, Valerie Schuman, Michael A. Teitell, Kenneth Dorshkind, Stephen T. Smale

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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 μ 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.

Original languageEnglish (US)
Pages (from-to)3508-3515
Number of pages8
JournalJournal of Immunology
Volume175
Issue number6
DOIs
StatePublished - Sep 15 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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