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 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.
Seimiya
Mika
M
Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
Bahar
Rumana
R
Wang
Yanqing
Y
Kawamura
Kiyoko
K
Tada
Yuji
Y
Okada
Seiji
S
Hatano
Masahiko
M
Tokuhisa
Takeshi
T
Saisho
Hiromitsu
H
Watanabe
Takeshi
T
Tagawa
Masatoshi
M
O-Wang
Jiyang
J
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D015536:Down-Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007075:Immunoglobulin M / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007075:Immunoglobulin M; D012333:RNA, Messenger; D019014:fas Receptor; C491539:Bhlhe40 protein, mouse