The absence of the transcription activator TFE3 impairs activation of B cells in vivo

Kevin Merrell, Sandra Wells, Andrew Henderson, James Gorman, Fred Alt, Alan Stall, Kathryn Calame

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop helix zipper transcription factors. TFE3 binds to μE3 sites located in the immunoglobulin heavy-chain (IgH) intronic enhancer, heavy- chain variable region promoters, the Ig kappa intronic enhancer, and regulatory sites in other genes. To understand the role of TFE3 in Ig expression and lymphoid development, we used embryonic stem (ES) cell- mediated gent targeting and RAG2(-/-) blastocyst complementation to generate mice which lack TFE3 in their B and T lymphocytes. TFE3- ES cells fully reconstitute the B- and T-cell compartments, giving rise to normal patterns of IgM+ B220+ B cells and CD4+ and CD8+ T cells. However, TFE3- B cells show several defects consistent with poor B-cell activation. Serum IgM levels are reduced twofold and IgG and IgA isotypes are reduced three- to sixfold in the TFE3- chimeras even though in vitro, the TFE3- splenocyte secrete normal levels of all isotypes in response to lipopolysaccharide activation. Peripheral TFE3- B cells also show reduced surface expression of CD23 and CD24 (heat-stable antigen).

Original languageEnglish (US)
Pages (from-to)3335-3344
Number of pages10
JournalMolecular and cellular biology
Volume17
Issue number6
DOIs
StatePublished - Jun 1997
Externally publishedYes

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