Clast5/Stra13 Is a Negative Regulator of B Lymphocyte Activation

CD40 is a member of the tumor necrosis factor receptor family and mediates a variety of functions of B cells, including B cell survival, proliferation, immunoglobulin gene class switching, memory B cell formation, and regulation of Fas-mediated apoptosis. To begin to elucidate the molecular mechanis...

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Published in:Biochemical and biophysical research communications 2002-03, Vol.292 (1), p.121-127
Main Authors: Seimiya, Mika, Bahar, Rumana, Wang, Yanqing, Kawamura, Kiyoko, Tada, Yuji, Okada, Seiji, Hatano, Masahiko, Tokuhisa, Takeshi, Saisho, Hiromitsu, Watanabe, Takeshi, Tagawa, Masatoshi, O-Wang, Jiyang
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Apoptosis
B-Lymphocytes - immunology
Basic Helix-Loop-Helix Transcription Factors
CD40
CD40L protein
Cell Cycle
Cell Division
Cell Nucleus - chemistry
Cells, Cultured
Clast5 gene
Down-Regulation
Fas
fas Receptor - metabolism
helix-loop-helix
Homeodomain Proteins - genetics
Homeodomain Proteins - physiology
Immunoglobulin M - immunology
Kinetics
Lymphocyte Activation
Lymphoma, B-Cell - metabolism
Mice
Mice, Inbred C57BL
proliferation
RNA, Messenger - biosynthesis
Stra13 gene
transcription factor
Transfection
Tumor Cells, Cultured
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Summary:CD40 is a member of the tumor necrosis factor receptor family and mediates a variety of functions of B cells, including B cell survival, proliferation, immunoglobulin gene class switching, memory B cell formation, and regulation of Fas-mediated apoptosis. To begin to elucidate the molecular mechanism governing such diverse functions of CD40, we have isolated a gene from mouse splenic B cells, termed Clast5, whose expression is strongly repressed during B cell activation. Clast5 is identical with Stra13, a recently identified member of the basic helix-loop-helix family of transcription factors. Clast5/Stra13 is highly expressed in unstimulated, resting B cells and is rapidly downregulated by a variety of stimuli that activate B cells, including CD40 ligand, anti-IgM antibodies, lipopolysaccharides and interleukin-4. Forced expression of Clast5/Stra13 in B cells delayed the cell cycle progression into S phase and strongly suppressed Fas-mediated apoptosis. Moreover, Clast5/Stra13 inhibited the colony formation in fibroblasts. Our results suggest that Clast5/Stra13 functions as a negative regulator of B cell activation by inhibiting cell cycle progression and cell growth.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2002.6605