The absence of the transcription activator TFE3 impairs activation of B cells in vivo.
TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop helix zipper transcription factors. TFE3 binds to muE3 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 gene 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- splenocytes 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).
Merrell
K
K
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Wells
S
S
Henderson
A
A
Gorman
J
J
Alt
F
F
Stall
A
A
Calame
K
K
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001854:Bone Marrow Cells; D002678:Chimera; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D018257:Helix-Loop-Helix Motifs; D016350:Leucine Zippers; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000502:physiology; D017455:Receptors, IgE / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D011506:Proteins; C499308:Rag2 protein, mouse; D017455:Receptors, IgE; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; C068486:Tcfe3 protein, mouse